bluuebunny/crossref_metadata_2025_split huggingface dataset:
Native Extracellular Matrix Orientation Determines Multipotent Vascular Stem Cell Proliferation in Response to Cyclic Uniaxial Tensile Strain and Simulated Stent Indentation
Authors: Mathieu P.S. , Fitzpatrick E. , Di Luca M. , Cahill P.A. , Lally C. 
Published: December 2020

AbstractCardiovascular disease is the leading cause of death worldwide, with multipotent vascular stem cells (MVSC) implicated in contributing to diseased vessels. MVSC are mechanosensitive cells which align perpendicular to cyclic uniaxial tensile strain. Within the blood vessel wall, collagen fibers constrain cells so that they are forced to align circumferentially, in the primary direction of tensile strain. In these experiments, MVSC were seeded onto the medial layer of decellularized porcine carotid arteries, then exposed to 10%, 1 Hz cyclic tensile strain for 10 days with the collagen fiber direction either parallel or perpendicular to the direction of strain. Cells aligned with the direction of the collagen fibers regardless of the orientation to strain. Cells aligned with the direction of strain showed an increased number of proliferative Ki67 positive cells, while those strained perpendicular to the direction of cell alignment showed no change in cell proliferation. A bioreactor system was designed to simulate the indentation of a single, wire stent strut. After 10 days of cyclic loading to 10% strain, MVSC showed regions of densely packed, highly proliferative cells. Therefore, MVSC may play a significant role in in-stent restenosis, and this proliferative response could potentially be controlled by controlling MVSC orientation relative to applied strain.
Radiochemical synthesis and evaluation in nonhuman primates of 3-[11C]methoxy-4-aminopyridine: a novel PET tracer for imaging potassium channels in the CNS
Authors: Guehl Nicolas J. , Neelamegam Ramesh , Zhou Yu-Peng , Moon Sung-Hyun , Dhaynaut Maeva , El Fakhri Georges , Normandin Marc D. , Brugarolas Pedro 
Published: December 2020

AbstractDemyelination, the loss of the protecting sheath of neurons, contributes to disability in many neurological diseases. In order to fully understand its role in different diseases and to monitor treatments aiming at reversing this process, it would be valuable to have PET radiotracers that can detect and quantify molecular changes involved in demyelination such as the uncovering and upregulation of the axonal potassium channels Kv1.1 and Kv1.2. Carbon-11 labeled radiotracers present the advantage of allowing for multiple scans on the same subject in the same day. Here, we describe [11C|3MeO4AP, a novel11C-labeled version of the K+channel tracer [18F]3F4AP, and characterize its imaging properties in two nonhuman primates including a monkey with a focal brain injury sustained during a surgical procedure three years prior to imaging. Our findings show that [11C]3MeO4AP is brain permeable, metabolically stable and has high plasma availability. When compared with [18F]3F4AP, [11C]3MeO4AP shows very high correlation in volumes of distribution (VT) confirming a common target. [11C]3MeO4AP shows slower washout than [18F]3F4AP suggesting stronger binding. Finally, similar to [18F]3F4AP, [11C]3MeO4AP is highly sensitive to the focal brain injury. All these features make it a promising radioligand for imaging demyelinated lesions.
Lifetime genealogical divergence within plants leads to epigenetic mosaicism in the long-lived shrubLavandula latifolia(Lamiaceae)
Authors: Herrera Carlos M. , Bazaga Pilar , Pérez Ricardo , Alonso Conchita 
Published: December 2020

SummaryEpigenetic mosaicism is a possible source of within-plant phenotypic heterogeneity, yet its frequency and developmental origin remain unexplored. This study examines whether the extant epigenetic heterogeneity within long-livedLavandula latifolia(Lamiaceae) shrubs reflects recent epigenetic modifications experienced independently by different plant parts or, alternatively, it is the cumulative outcome of a steady lifetime process.Leaf samples from different architectural modules were collected from threeL. latifoliaplants and characterized epigenetically by global DNA cytosine methylation and methylation state of methylation-sensitive amplified fragment length polymorphism markers (MS-AFLP). Epigenetic characteristics of modules were then assembled with information on the branching history of plants. Methods borrowed from phylogenetic research were used to assess genealogical signal of extant epigenetic variation and reconstruct within-plant genealogical trajectory of epigenetic traits.Plants were epigenetically heterogeneous, as shown by differences among modules in global DNA methylation and variation in the methylation states of 6-8% of MS-AFLP markers. All epigenetic features exhibited significant genealogical signal within plants. Events of epigenetic divergence occurred throughout the lifespan of individuals and were subsequently propagated by branch divisions.Internal epigenetic diversification ofL. latifoliaindividuals took place steadily during their development, a process which eventually led to persistent epigenetic mosaicism.
The essential role of sodium bioenergetics and ATP homeostasis in the developmental transitions of a cyanobacterium
Authors: Doello Sofia , Burkhardt Markus , Forchhammer Karl 
Published: December 2020

AbstractThe ability to resume growth after a dormant period is an important strategy for the survival and spreading of bacterial populations. Energy homeostasis is critical in the transition into and out of a quiescent state. Synechocystis sp. PCC 6803, a non-diazotrophic cyanobacterium, enters metabolic dormancy as a response to nitrogen starvation. We used Synechocystis as a model to investigate the regulation of ATP homeostasis during dormancy and unraveled a critical role for sodium bioenergetics in dormant cells. During nitrogen starvation, cells reduce their ATP levels and engage sodium bioenergetics to maintain the minimum ATP content required for viability. When nitrogen becomes available, energy requirements rise, and cells immediately increase ATP levels employing sodium bioenergetics and glycogen catabolism. These processes allow them to restore the photosynthetic machinery and resume photoautotrophic growth. Our work reveals a precise regulation of the energy metabolism essential for bacterial survival during periods of nutrient deprivation.
Glycomic analysis reveals a conserved response to bacterial sepsis induced by different bacterial pathogens
Authors: Heindel Daniel W. , Aziz Peter V. , Chen Shuhui , Marth Jamey D. , Mahal Lara K. 
Published: December 2020

AbstractSepsis is an extreme inflammatory response to infection (bacterial, viral, fungal) that occurs in the bloodstream and causes damage throughout the body. Currently, there are few diagnostic biomarkers of sepsis and new effective treatments have not been developed. There is a clear need to study the molecular underpinnings of this disease. Glycosylation is known to play a role in immunity and inflammation, but the role of glycans in sepsis is not well defined. Herein, we profiled the serum glycomes of experimental mouse sepsis models to identify changes induced by 4 different clinical bacterial pathogens (Gram-positive:Streptococcus pneumoniae, Staphylococcus aureus, Gram-negative:Escherichia coliandSalmonellaTyphimurium) using our lectin microarray technology. We observed global shifts in the blood sera glycome that were conserved across all four species, regardless of whether they were Gram positive or negative. Bisecting GlcNAc was decreased upon sepsis and a strong increase in core 1/3O-glycans was observed. Lectin blot analysis revealed a high molecular weight protein induced in sepsis by all four bacteria as the major cause of the core 1/3O-glycan shift. While the identity of this protein remains to be elucidated, its presence indicates a common feature of bacterial sepsis associated with this glycomic signature.
Rapid encoding of temporal sequences discovered in brain dynamics
Authors: Bonetti L. , Brattico E. , Carlomagno F. , Donati G. , Cabral J. , Haumann N.T. , Deco G. , Vuust P. , Kringelbach M.L. 
Published: December 2020

ABSTRACTInformation encoding has received a wide neuroscientific attention, but the underlying rapid spatiotemporal brain dynamics remain largely unknown. Here, we investigated the rapid brain mechanisms for encoding and prediction of sounds forming a complex temporal sequence. Specifically, we used magnetoencephalography (MEG) to record the brain activity of 68 participants while they listened to a highly structured musical prelude. Advanced analysis of the phase synchronisation and graph theoretical measures showed the rapid transition of brain activity from primary auditory cortex to higher order association areas including insula and superior temporal pole within a whole-brain network, occurring during the first 220 ms of the encoding process. We discovered individual differences, revealing the rapid unfolding of brain network dynamics responsible for the processing of the current sounds and the prediction of the forthcoming events of the sequence. This provides a first glimpse of the general mechanisms underlying pattern encoding in the human brain.
The transcriptomic landscapes of diverse rice cultivars grown under mild drought conditions
Authors: Kawakatsu Taiji , Teramoto Shota , Takayasu Satoko , Maruyama Natsuko , Nishijima Ryo , Kitomi Yuka , Uga Yusaku 
Published: December 2020

ABSTRACTRoot system architecture affects plant drought tolerance and other key agronomic traits such as lodging. However, although phenotypic and genomic variation has been extensively analyzed, few field studies have integrated phenotypic and transcriptomic information, especially for below-ground traits such as root system architecture. Here, we report the phenotypic and transcriptomic landscape of 61 rice (Oryza sativa) accessions with highly diverse below-ground traits grown in an upland field under mild drought stress. We found that four principal components explained the phenotypic variation and that accessions could be classified into four admixture groups (admixed,aus,indica, andjaponica) based on their tiller numbers and crown root diameters. Transcriptome analysis revealed that differentially expressed genes associated with specific admixture groups were enriched with stress response-related genes, suggesting that admixture groups have distinct stress response mechanisms. Root growth was negatively correlated with auxin-inducible genes, suggesting an association between auxin signaling and mild drought stress. A negative correlation between crown root diameter and stress response-related genes suggested that thicker crown root diameter is associated with resistance to mild drought stress. Finally, co-expression network analysis implemented with DNA affinity purification followed by sequencing (DAP-seq) analysis identified phytohormone signaling networks and key transcription factors negatively regulating crown root diameter. Our datasets provide a useful resource for understanding the genomic and transcriptomic basis of phenotypic variation under mild drought stress.ONE-SENTENCE SUMMARYCatalog of the phenomes and transcriptomes of rice cultivars grown in upland fields provides a resource for further studies toward breeding climate-resilient crops.
Physiological and transcriptomic response ofMedicago truncatulato colonization with high and low benefit arbuscular mycorrhizal fungi
Authors: Cope Kevin R. , Kafle Arjun , Yakha Jaya K. , Pfeffer Philip E. , Strahan Gary D. , Garcia Kevin , Subramanian Senthil , Bücking Heike 
Published: December 2020

ABSTRACTArbuscular mycorrhizal (AM) fungi form a root endosymbiosis with many agronomically important crop species and both enhance the ability of their host to obtain nutrients from the soil and increase host tolerance to biotic and abiotic stressors. However, AM fungal species differ in the benefits they provide to their host plants. Here, we examined the putative molecular mechanisms involved in the regulation of the physiological response ofMedicago truncatulato eitherRhizophagus irregularis or Glomus aggregatum,a high or a low benefit AM fungus, respectively. Colonization withR. irregularisled to higher growth and nutrient uptake benefits than the colonization withG. aggregatum. These benefits were linked to an elevated expression in the roots of genes involved in strigolactone biosynthesis (NSP1,NSP2,CCD7, andMAX1a), mycorrhiza-induced phosphate (PT8), ammonium (AMT2;3), and nitrate (NPF4.12) transporters and the putative ammonium transporterNIP1;5.R. irregularisalso stimulated the expression of photosynthesis-related genes in the shoot and the upregulation of the sugar transportersSWEET1.2, SWEET3.3andSWEET 12and the lipid biosynthesis geneRAM2in the roots. In contrast,G. aggregatuminduced the expression of biotic stress defense response genes in the shoots and several genes associated with abiotic stress in the roots. This suggests that either the host perceives colonization byG. aggregatumas a pathogen attack or thatG. aggregatumcan prime host defense responses. Our findings reveal novel insights into the molecular mechanisms that control the host plant response to colonization with high- and low-benefit arbuscular mycorrhizal fungal symbionts.
Importance of test-retest reliability for promoting fMRI based screening and interventions in major depressive disorder
Authors: Compère Laurie , Siegle Greg J. , Young Kymberly 
Published: December 2020

AbstractProponents of personalized medicine have promoted neuroimaging evaluation and treatment of major depressive disorder in three areas of clinical application: clinical prediction, outcome evaluation, and neurofeedback. Whereas psychometric considerations such as test-retest reliability are basic precursors to clinical adoption for most clinical instruments, they are often not considered for neuroimaging assessments. As an example, we consider functional magnetic resonance imaging (fMRI) of depression, a common and particularly well validated mechanistic technology for understanding disorder and guiding treatment. In this article, we review work on test-retest reliability for depression fMRI studies. We find that basic psychometrics have not been regularly attended to in this domain. For instance, no fMRI neurofeedback study has included measures of test-retest reliability despite the implicit assumption that brain signals are stable enough to train. We consider several factors that could be useful to aid clinical translation including 1) attending to how the BOLD response is parameterized, 2) identifying and promoting regions or voxels with stronger psychometric properties 3) accounting for within-individual changes (e.g., in symptomatology) across time and 4) focusing on tasks and clinical populations that are relevant for the intended clinical application. We apply these principles to published prognostic and neurofeedback data sets. The broad implication of this work is that attention to psychometrics is important for clinical adoption of mechanistic assessment, is feasible, and may improve the underlying science.
Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations
Authors: Bottaro Sandro , Bussi Giovanni , Lindorff-Larsen Kresten 
Published: December 2020

AbstractThe 5′ untranslated region (UTR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structures are not known yet. Here, we predict structure and dynamics of five RNA stem loops in the 5′-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrangements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterisation of these systems, and provide putative three-dimensional models for structure-based drug design studies.
A novel allele ofSIR2reveals a heritable intermediate state of gene silencing
Authors: Farris Delaney , Saxton Daniel S , Rine Jasper 
Published: December 2020

AbstractGenetic information acquires additional meaning through epigenetic regulation, the process by which genetically identical cells can exhibit heritable differences in gene expression and phenotype. Inheritance of epigenetic information is a critical step in maintaining cellular identity and organismal health. InSaccharomyces cerevisiae, one form of epigenetic regulation is the transcriptional silencing of two mating-type loci,HMLandHMR, by the SIR-protein complex. To focus on the epigenetic dimension of this gene regulation, we conducted a forward mutagenesis screen to identify mutants exhibiting an epigenetic or metastable silencing defect. We utilized fluorescent reporters atHMLandHMR, and screened yeast colonies for epigenetic silencing defects. We uncovered numerous independentsir1alleles, a gene known to be required for stable epigenetic inheritance. More interestingly, we recovered a missense mutation withinSIR2, which encodes a highly conserved histone deacetylase. In contrast tosir1Δ, which exhibits states that are either fully silenced or fully expressed, thissir2allele exhibited heritable states that were either fully silenced or expressed at an intermediate level. The heritable nature of this unique silencing defect was influenced by, but not completely dependent on, changes in rDNA copy number. Therefore, this study revealed a heritable state of intermediate silencing and linked this state to a central silencing factor, Sir2.
Evolution of the recombination regulator PRDM9 in minke whales
Authors: Damm Elena , Ullrich Kristian K , Amos William B , Odenthal-Hesse Linda 
Published: December 2020

AbstractWe explored the structure and variability of thePrdm9gene, which codes for the PRDM9 protein, in samples of the minke whales from the Atlantic, Pacific and Southern Oceans. The PRDM9 protein controls the reshuffling of parental genomes in most metazoans and we show that minke whale possess all the features characteristic of PRDM9-directed recombination initiation, including complete KRAB, SSXRD and SET domains and a rapidly evolving array of C2H2-type-Zincfingers (ZnF). We uncovered eighteen novel PRDM9 variants and evidence of rapid evolution, particularly at DNA-recognizing positions that evolve under positive selection. At different geographical scales, we observed extensivePrdm9allelic diversity in Antarctic minke whales (Balaenoptera bonarensis) that, conversely, lack observable population differentiation in mitochondrial DNA and microsatellites. In contrast, a single PRDM9 variant is shared between all Common Minke whales and even across subspecies boundaries of North Atlantic (B. a. acutorostrata) and North Pacific (B. a. scammoni) minke whale, which do show clear population differentiation. PRDM9 variation of whales predicts distinct recombination initiation landscapes genome-wide, which has possible consequences for speciation.
Measuring Compound Eye Optics with Microscope and MicroCT Images
Authors: Currea John Paul , Sondhi Yash , Kawahara Akito Y. , Theobald Jamie 
Published: December 2020

AbstractWith a great variety of shapes and sizes, compound eye morphologies give insight into visual ecology, development, and evolution, and inspire novel engineering. In contrast to our owncamera-typeeyes, compound eyes reveal their resolution, sensitivity, and field of view externally, provided they have spherical curvature and orthogonal ommatidia. Non-spherical compound eyes with skewed ommatidia require measuring internal structures, such as with MicroCT (μCT). Thus far, there is no efficient tool to characterize compound eye optics, from either 2D or 3D data, automatically. Here we present two open-source programs: (1) the ommatidia detecting algorithm (ODA), which measures ommatidia count and diameter in 2D images, and (2) a μCT pipeline (ODA-3D), which calculates anatomical acuity, sensitivity, and field of view across the eye by applying the ODA to 3D data. We validate these algorithms on images, images of replicas, and μCT eye scans from ants, fruit flies, moths, and a bee.
Choice of fluorophore affects dynamic DNA nanostructures
Authors: Jahnke Kevin , Grubmüller Helmut , Igaev Maxim , Göpfrich Kerstin 
Published: December 2020

AbstractThe ability to dynamically remodel DNA origami structures or functional nanodevices is highly desired in the field of DNA nanotechnology. Concomitantly, the use of fluorophores to track and validate the dynamics of such DNA-based architectures is commonplace and often unavoidable. It is therefore crucial to be aware of the side effects of popular fluorophores, which are often exchanged without considering the potential impact on the system. Here, we show that the choice of fluorophore can strongly affect the reconfiguration of DNA nanostructures. To this end, we encapsulate a triple-stranded DNA (tsDNA) into water-in-oil compartments and functionalize their periphery with a single-stranded DNA handle (ssDNA). Thus, the tsDNA can bind and unbind from the periphery by reversible opening of the triplex and subsequent strand displacement. Using a combination of experiments, molecular dynamics (MD) simulations, and reaction-diffusion modeling, we demonstrate for twelve different fluorophore combinations that it is possible to alter or even inhibit the DNA nanostructure formation – without changing the DNA sequence. Besides its immediate importance for the design of pH-responsive switches and fluorophore labelling, our work presents a strategy to precisely tune the energy landscape of dynamic DNA nanodevices.
Health education teachers' historical bodies: constructing teacher identity and teaching information evaluation
Authors: Nygård Tuula , Hirvonen Noora , Räisänen Sari , Korkeamäki Riitta-Liisa 
Published: December 2020

PurposeThis article describes how Finnish health education teachers verbalise and construct their teacher identity based on their lifestyle, subject area and relationships with their students.Design/methodology/approachNarrative interviews were conducted amongst eight secondary and upper secondary school teachers. The nexus analysis was used to analyse teachers' methods of teaching students information-seeking, evaluation and critical thinking skills.FindingsThe teachers' historical bodies – their skills, interests, information-seeking habits and familiar sources – impacted the chosen teaching methods. The results indicate that teacher identity is constructed along different paths and is constantly performed and transformed in the classroom through interactions with students.Originality/valueThe study illustrates the reconstruction of teacher identity through interaction in interviews. Teachers act as role models, information gatekeepers and trustees who guide students to choose credible health information sources.