Full versions of all publications can be downloaded by clicking on the titles.
Nature Nanotechnology
Dynamic switching of the spin circulation in tapered magnetic nanodisks
Uhlíř, V.; Urbánek, M.; Hladík, L.; Spousta, J.; Im, M-Y.; Fisher, P.; Eibagi, N.; Kan, J.; Fullerton, E.; Šikola, T.
Research Group: Fabrication and Characterisation of Nanostructures
Research Programme: Advanced Nanotechnologies and Microtechnologies
Summary
Magnetic vortices are characterized by the sense of in-plane magnetization circulation and by the polarity of the vortex core. With each having two possible states, there are four possible stable magnetization configurations that can be utilized for a multibit memory cell. Dynamic control of vortex core polarity has been demonstrated using both alternating and pulsed magnetic fields and currents. Here, we show controlled dynamic switching of spin circulation in vortices using nanosecond field pulses by imaging the process with full-field soft X-ray transmission microscopy. The dynamic reversal process is controlled by far-from-equilibrium gyrotropic precession of the vortex core, and the reversal is achieved at significantly reduced field amplitudes when compared with static switching. We further show that both the field pulse amplitude and duration required for efficient circulation reversal can be controlled by appropriate selection of the disk geometry.
Composites Science and Technology
The shear adhesion strength between the FRC substructure and denture base resin: Effects of FRC architecture, adhesive composition and hydrolytic degradation
Poláček, P.; Salajková, M.; Jančář, J.
Research Group: Advanced Polymers and Composites
Research Programme: Advanced Materials
Summary
The adhesion strength between fiber reinforced composite (FRC) members and denture-base resin is pivotal for enhancing removable denture long lasting performance and patient comfort. FRC reinforcing rods based on glass fibers impregnated with light curing resin were used to model the FRC substructure. The influence of fiber architecture and adhesive layer composition on the shear adhesion strength, τa, between the FRC and denture-base resin was investigated both dry and in moist environment to assess the stability of the adhesive bond in the oral cavity. The obtained results suggest that for a given fiber architecture, adhesive composition and test conditions, the wetting of the FRC surface was the primary variable affecting the τa. In the case of good wetting and formation of adhesive bond between the substrates, interlaminar shear strength of the unidirectional FRC substrate was the limiting factor. In multidirectional FRC substrate, the shear strength of the outer resin rich layer was limiting factor for the maximum adhesion strength.
JCTC – Journal of Chemical Theory and Computation
Toward Reproducing Sequence Trends in Phosphorus Chemical Shifts for Nucleic Acids by MD/DFT Calculations
Přecechtělová, J.; Munzarová, M.L.; Vaara, J.; Novotný, J.; Dračínský, M.; Sklenář, V.
Research Group: Biomolecular NMR Spectroscopy
Research Programme: Structural Biology
Summary
This work addresses the question of the ability of the molecular dynamics–density functional theory (MD/DFT) approach to reproduce sequence trend in 31P chemical shifts (δP) in the backbone of nucleic acids. δP for [d(CGCGAATTCGCG)]2, a canonical B-DNA, have been computed using density functional theory calculations on model compounds with geometries cut out of snapshots of classical molecular dynamics (MD) simulations. The values of 31P chemical shifts for two distinct B-DNA subfamilies BI and BII, δP/BI and δP/BII, have been determined as averages over the BI and BII subparts of the MD trajectory. This has been done for various samplings of MD trajectory and for two sizes of both the model and the solvent embedding. For all of the combinations of trajectory sampling, model size, and embedding size, sequence dependence of δP/BI in the order of 0.4–0.5 ppm has been obtained. Weighted averages for individual 31P nuclei in the studied DNA double-helix have been calculated from δP/BI and δP/BII using BI and BII percentages from free MD simulations as well as from approaches employing NMR structural restraints. A good qualitative agreement is found between experimental sequence trends in δP and theoretical δP employing short (24 ns) MD run and BI, BII percentages determined by Hartmann et al. or via MD with the inclusion of NMR structural restraints. Theoretical δP exhibit a systematic offset of ca. 11 ppm and overestimation of trends by a factor of ca. 1.7. When scaled accordingly, theoretical δP/BI and δP/BII can be used to determine the expected percentage of BII to match the experimental value of δP. As evidenced by the calculations on snapshots from Car–Parrinello molecular dynamics, the systematic offsets of the theoretical δP obtained by MD/DFT approach result primarily from the unrealistic bond lengths employed by classical MD. The findings made in this work provide structure−δP relationships for possible use as NMR restraints and suggest that NMR calculations on MD snapshots can be in the future employed for the validation of newly developed force fields.
Chemistry – A European Journal
A QM/MM Investigation of the Catalytic Mechanism of Metal-Ion-Independent Core 2 β1,6-N-Acetylglucosaminyltransferase
Tvaroška, I.;Kozmon, S.;Wimmerová, M.;Koča, J.
Research Groups: Glycobiochemistry & Computational Chemistry
Research Programme: Structural Biology
Summary
β1,6-GlcNAc-transferase (C2GnT) is an important controlling factor of biological functions for many glycoproteins and its activity has been found to be altered in breast, colon, and lung cancer cells, in leukemia cells, in the lymhomonocytes of multiple sclerosis patients, leukocytes from diabetes patients, and in conditions causing an immune deficiency. The result of the action of C2GnT is the core 2 structure that is essential for the further elongation of the carbohydrate chains of O-glycans. The catalytic mechanism of this metal-ion-independent glycosyltransferase is of paramount importance and is investigated here by using quantum mechanical (QM) (density functional theory (DFT))/molecular modeling (MM) methods with different levels of theory. The structural model of the reaction site used in this report is based on the crystal structures of C2GnT. The entire enzyme–substrate system was subdivided into two different subsystems: the QM subsystem containing 206 atoms and the MM region containing 5914 atoms. Three predefined reaction coordinates were employed to investigate the catalytic mechanism. The calculated potential energy surfaces discovered the existence of a concerted SN2-like mechanism. In this mechanism, a nucleophilic attack by O6 facilitated by proton transfer to the catalytic base and the separation of the leaving group all occur almost simultaneously. The transition state for the proposed reaction mechanism at the M06-2X/6-31G** (with diffuse functions on the O1’, O5’, OGlu, and O6 atoms) level was located at C1-O6=1.74 Å and C1-O1=2.86 Å. The activation energy for this mechanism was estimated to be between 20 and 29 kcalmol-1, depending on the method used. These calculations also identified a low-barrier hydrogen bond between the nucleophile O6H and the catalytic base Glu320, and a hydrogen bond between the N-acetamino group and the glycosidic oxygen of the donor in the TS. It is proposed that these interactions contribute to a stabilization of TS and participate in the catalytic mechanism.
The Plant Cell
Deciphering the Diploid Ancestral Genome of the Mesohexaploid Brassica rapa
Cheng, F.; Mandáková, T.; Wu, J.; Xie, Q.; Lysak, M.A.; Wang, X.
Research Group: Plant Cytogenomics
Research Programme: Genomics and Proteomics of Plant Systems
Summary
The genus Brassica includes several important agricultural and horticultural crops. Their current genome structures were shaped by whole-genome triplication followed by extensive diploidization. The availability of several crucifer genome sequences, especially that of Chinese cabbage (Brassica rapa), enables study of the evolution of the mesohexaploid Brassica genomes from their diploid progenitors. We reconstructed three ancestral subgenomes of B. rapa (n = 10) by comparing its whole-genome sequence to ancestral and extant Brassicaceae genomes. All three B. rapa paleogenomes apparently consisted of seven chromosomes, similar to the ancestral translocation Proto-Calepineae Karyotype (tPCK; n = 7), which is the evolutionarily younger variant of the Proto-Calepineae Karyotype (n = 7). Based on comparative analysis of genome sequences or linkage maps of Brassica oleracea, Brassica nigra, radish (Raphanus sativus), and other closely related species, we propose a two-step merging of three tPCK-like genomes to form the hexaploid ancestor of the tribe Brassiceae with 42 chromosomes. Subsequent diversification of the Brassiceae was marked by extensive genome reshuffling and chromosome number reduction mediated by translocation events and followed by loss and/or inactivation of centromeres. Furthermore, via interspecies genome comparison, we refined intervals for seven of the genomic blocks of the Ancestral Crucifer Karyotype (n = 8), thus revising the key reference genome for evolutionary genomics of crucifers.
European Journal of Immunology
Pairing of T-cell receptor chains via emulsion PCR
Turchaninova, M.A.; Britanova, O.V.; Bolotin, D.A.; Shugay, M.; Putintseva, E.V.; Staroverov, D.B.; Sharonov, G.; Shcherbo, D.; Zvyagin, I.V.; Mamedov, I.Z.; Linnemann, C.; Schumacher, T.N.; Chudakov, D.M.
Research Group: Adaptive Immunity Group
Research Programme: Molecular Medicine
Summary
Our ability to analyze adaptive immunity and engineer its activity has long been constrained by our limited ability to identify native pairs of heavy-light antibody chains and alpha-beta T-cell receptor (TCR) chains – both of which comprise coupled “halves of a key”, collectively capable of recognizing specific antigens. Here we report a cell-based emulsion RT-PCR approach that allows the selective fusion of the native pairs of amplified TCR alpha and beta chain genes for complex samples. A new type of PCR suppression technique was developed that makes it possible to amplify the fused library with minimal noise for subsequent analysis by high-throughput paired end Illumina sequencing. With this technique, single analysis of a complex blood sample allows identification of multiple native TCR chain pairs. This approach may be extended to identify native antibody chain pairs and, more generally, pairs of mRNA molecules that are co-expressed in the same living cells.
Genome Biology and Evolution
Contrasting patterns of transposable element and satellite distribution on sex chromosomes (XY1Y2) in the dioecious plant Rumex acetosa
Steflova, P.; Tokan, V.; Vogel, I.; Lexa, M.; Macas, J.; Novak, P.; Hobza, R.; Vyskot, B.; Kejnovsky, E.
Research Group: Genome Dynamics
Research Programme: Molecular Medicine
Summary
Rumex acetosa is a dioecious plant with the XY1Y2 sex chromosome system. Both Y chromosomes are heterochromatic and are thought to be degenerated. We performed low-pass 454 sequencing and similarity-based clustering of male and female genomic 454 reads in order to identify and characterize major groups of R. acetosa repetitive DNA. We found that Copia and Gypsy retrotransposons dominated, followed by DNA transposons and non-LTR retrotransposons. CRM and Tat/Ogre retrotransposons dominated the Gypsy superfamily while Maximus/Sireviruses were most abundant among Copia retrotransposons. Only one Gypsy subfamily had accumulated on Y1 and Y2 chromosomes while many retrotransposons were ubiquitous on autosomes and the X chromosome, but absent on Y1 and Y2 chromosomes, and others were depleted from the X chromosome. One group of CRM Gypsy was specifically localized to centromeres. We also found that majority of previously described satellites (RAYSI, RAYSII, RAYSIII, RAE180) are accumulated on the Y chromosomes where we identified Y chromosome-specific variant of RAE180. We discovered two novel satellites - RA160 satellite dominating on the X chromosome, and RA690 localized mostly on the Y1 chromosome. The expression pattern obtained from Illumina RNA sequencing showed that the expression of transposable elements is similar in leaves of both sexes and that satellites are also expressed. Contrasting patterns of TEs and satellite localization on sex chromosomes in R. acetosa, where not only accumulation but also depletion of repetitive DNA was observed, suggesting that a plethora of evolutionary processes can shape sex chromosomes.
Pharmacology &Therapeutics
Endocannabinoid system and mood disorders: Priming a target for new therapies
Micale, V.; Di Marzo, V.; Sulcova, A.; Wotjak, C.T.; Drago, F.
Research Group: Experimental and Applied Neuropsychopharmacology
Research Programme: Brain and Mind Research
Summary:
The endocannabinoid system comprising the cannabinoid receptor systems and their endogenous ligands is strongly involved in neuropsychiatric disorders, particularly in affective disturbances such as anxiety and depression. There are discussed in this review article, scientific suggestions how synthetic molecules that interact with the activity the endocannabinoid system can open the way to new multi-target therapeutic strategies in mood disorders.
Human Brain Mapping
Brain functional connectivity of male patients in remission after the first episode of schizophrenia
Kasparek, T.; Prikryl, R.; Rehulova, J.; Marecek, R.; Mikl, M.; Prikrylova, H.; Vanicek, J.; Ceskova, E.
Research Group: Behavioural and Social Neuroscience
Research Programme: Brain and Mind Research
Summary:
Objectives: Abnormal task-related activation and connectivity is present in schizophrenia. The aim of this study was the analysis of functional networks in schizophrenia patients in remission after the first episode. Experimental design: Twenty-nine male patients in remission after the first episode of schizophrenia and 22 healthy controls underwent examination by functional magnetic resonance during verbal fluency tasks (VFT). The functional connectivity of brain networks was analyzed using independent component analysis. Results: The patients showed lower activation of the salience network during VFT. They also showed lower deactivation of the default mode network (DMN) during VFT processing. Spectral analysis of the component time courses showed decreased power in slow frequencies of signal fluctuations in the salience and DMNs and increased power in higher frequencies in the left frontoparietal cortex reflecting higher fluctuations of the network activity. Moreover, there was decreased similarity of component time courses in schizophrenia—the patients had smaller negative correlation between VFT activated and deactivated networks, and smaller positive correlations between DMN subcomponents. Conclusions: There is still an abnormal functional connectivity of several brain networks in remission after the first episode of schizophrenia. The effect of different treatment modalities on brain connectivity, together with temporal dynamics of this functional abnormality should be the objective of further studies to assess its potential as a marker of disease stabilization.
Plos Neglected Tropical Diseases
Novel insights into the genetic diversity of Balantidium and Balantidium-like cyst-forming ciliates
Pomajbíková, K.; Oborník, M.; Horák, A.; Petrželková, K.J.; Grim, J.N.; Levecke, B.; Todd, A.; Mulama, M.; Kiyang, J.; Modrý, D.
Research Group: Parasitology
Research Programme: Molecular Veterinary Medicine
Summary
Balantidiasis is considered a neglected zoonotic disease with pigs serving as reservoir hosts. However, Balantidium coli has been recorded in many other mammalian species, including primates. Here, we evaluated the genetic diversity of B. coli in non-human primates using two gene markers (SSrDNA and ITS1-5.8SDNA-ITS2). We analyzed 49 isolates of ciliates from fecal samples originating from 11 species of captive and wild primates, domestic pigs and wild boar. The phylogenetic trees were computed using Bayesian inference and Maximum likelihood. Balantidium entozoon from edible frog and Buxtonella sulcata from cattle were included in the analyses as the closest relatives of B. coli, as well as reference sequences of vestibuliferids. The SSrDNA tree showed the same phylogenetic diversification of B. coli at genus level as the tree constructed based on the ITS region. Based on the polymorphism of SSrDNA sequences, the type species of the genus, namely B. entozoon, appeared tobe phylogenetically distinct from B. coli. Thus, we propose a new genus Neobalantidium for the homeothermic clade. Moreover, several isolates from both captive and wild primates (excluding great apes) clustered with B. sulcata with high support, suggesting the existence of a new species within this genus. The cysts of Buxtonella and Neobalantidium are morphologically indistinguishable and the presence of Buxtonella-like ciliates in primates opens the question about possible occurrence of these pathogens in humans.
PLoS One
Natural Killer Cell Receptor Genes in the Family Equidae: Not only Ly49
Futas, J.;Horin, P.
Research Group: Animal Immunogenomic
Research Programme: Molecular Veterinary Medicine
Summary
Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA)and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes.
