bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCF7L1 and TCF7 differentially regulate specific mouse ES cell genes in response to GSK-3 inhibition
Authors: Moreira Steven , Seo Caleb , Polena Enio , Mahendram Sujeivan , Mercier Eloi , Blais Alexandre , Doble Bradley W. 
Published: November 2018

The genome-wide chromatin occupancy of the TCF/LEF factors and its modulation by Wnt pathway activation remain poorly defined. Here, we describe mouse ES cell (mESC) lines expressing a single copy knock-in of the 3xFLAG epitope at the N-terminus of TCF7L1 and TCF7, the two most-highly expressed TCF/LEF factors in mESCs. TCF7L1 protein levels, detected by immunoblotting with a FLAG antibody, were much higher than TCF7 in mESCs maintained in standard serum- and LIF-supplemented medium, even in the presence of the GSK-3 inhibitor, CHIR99021 (CHIR). We used FLAG antibody-mediated ChIP-seq to determine TCF7 and TCF7L1 chromatin occupancy in mESCs cultured in standard medium with or without CHIR for 14 hours. TCF7 and TCF7L1 displayed very few overlapping ChIP peaks across the genome, with TCF7L1 binding significantly more genes than TCF7 in both culture conditions. Despite a reduction in total TCF7L1 protein after CHIR treatment, the TCF7L1 ChIP peak profiles were not uniformly attenuated. Our data demonstrate that TCF7L1 chromatin occupancy upon short-term CHIR treatment is modulated in a target-specific manner. Our findings also suggest that Wnt target genes in mESCs are not regulated by TCF/LEF switching, and TCF7L1, although often called a constitutive repressor, may serve as a transcriptional activator of certain target genes in CHIR-treated mESCs.HighlightsChIP and cytometry data suggest that TCF7L1 does not directly regulate mESC Nanog expression.TCF7L1 remains associated with β-catenin in the presence of CHIR99021.TCF7 and TCF7L1 display different chromatin occupancies in mESCs.TCF7L1 binding at specific genomic sites is variably altered by CHIR99021.
Waving goodbye to contrast: Self-generated hand movements attenuate visual sensitivity
Authors: Vasser Madis , Vuillaume Laurène , Cleeremans Axel , Aru Jaan 
Published: November 2018

AbstractIt is well known that the human brain continuously predicts the sensory consequences of its own body movements, which typically results in sensory attenuation. Yet, the extent and exact mechanisms underlying sensory attenuation are still debated. To explore this issue, we asked participants to decide which of two visual stimuli was of higher contrast in a virtual reality situation where one of the stimuli could appear behind the participants’ invisible moving hand or not. Over two experiments, we measured the effects of such “virtual occlusion” on first-order sensitivity and on metacognitive monitoring. Our findings show that self-generated hand movements reduced the apparent contrast of the stimulus. This result can be explained by the active inference theory. Moreover, sensory attenuation seemed to affect only first-order sensitivity and not (second-order) metacognitive judgments of confidence.
Crown defoliation decreases reproduction and wood growth in a marginal European beech population
Authors: Oddou-Muratorio Sylvie , Petit-Cailleux Cathleen , Journé Valentin , Lingrand Matthieu , Magdalou Jean-André , Hurson Christophe , Garrigue Joseph , Davi Hendrik , Magnanou Elodie 
Published: November 2018

ABSTRACTAbiotic and biotic stresses related to climate change have been associated to increased crown defoliation, decreased growth and a higher risk of mortality in many forest tree species, but the impact of stresses on tree reproduction and forest regeneration remains understudied. At dry, warm margin of species distributions, flowering, pollination and seed maturation processes are expected to be affected by drought, late frost and other stresses, eventually resulting in reproduction failure. Moreover, inter-individual variations in reproductive performances versus other performances (growth, survival) could have important consequences on population’s dynamics.We investigated the relationships between individual crown defoliation, growth and reproduction in a drought-prone population of European beech, Fagus sylvatica. We used a spatially explicit mating model and marker-based parentage analyses to estimate effective female and male fecundities of 432 reproductive trees, which were also monitored for basal area increment and crown defoliation over nine years.Female and male fecundities markedly varied among individuals, more than did growth. Both female fecundity and growth decreased with increasing crown defoliation and competition and increased with size. Male fecundity only responded to competition, and decreased with increasing competition. Moreover, the negative effect of defoliation on female fecundity was size-dependent, with a slower decline in female fecundity with increasing defoliation for the large individuals. Finally, a trade-off between growth and female fecundity was observed in response to defoliation: some large trees maintained significant female fecundity at the expense of reduced growth in response to defoliation, while some other defoliated trees rather maintained high growth at the expense of reduced female fecundity.Synthesis. Our results suggest that while decreasing their growth, some large defoliated trees still contribute to reproduction through seed production and pollination. This non-coordinated decline of growth and fecundity at individual-level in response to stress may compromise the evolution of stress-resistance traits at population level, and increase forest tree vulnerability.
Neurovascular coupling preserved in a chronic mouse model of Alzheimer’s disease: Methodology is critical
Authors: Sharp Paul S , Ameen-Ali Kam , Boorman Luke , Harris Sam , Wharton Stephen , Howarth Clare , Redgrave Peter , Berwick Jason 
Published: November 2018

AbstractNeurovascular coupling is the process by which neural activity causes localised changes in cerebral blood flow. Impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimer’s disease (AD), and if so, could serve as an early biomarker of cerebral pathology. We have established an anaesthetic regime in which evoked hemodynamic responses are comparable to those in awake mice. This protocol was adapted to allow repeated measurements of neurovascular function over three months in the hAPP-J20 mouse model of AD (J20-AD) and wild-type (WT) controls. Animals were 9-12 months old at the start of the experiment, which is when deficits due to the disease condition would be expected. Mice were chronically prepared with a cranial window through which optical imaging spectroscopy (OIS) was used to generate functional maps of the cerebral blood volume and saturation changes evoked by whisker stimulation and vascular reactivity challenges. Unexpectedly, the hemodynamic responses were largely preserved in the J20-AD group. This result failed to confirm previous investigations using the J20-AD model. However, a final acute electrophysiology and OIS experiment was performed to measure both neural and hemodynamic responses concurrently. In this experiment, previously reported deficits in neurovascular coupling in the J20-AD model were observed. This suggests that J20-AD mice may be more susceptible to the physiologically stressing conditions of an acute experimental procedure compared to WT animals. These results therefore highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.Significance StatementUsing a chronic anaesthetised preparation, we measured hemodynamic responses evoked by sensory stimulation and respiratory gases in the J20-AD mouse model of Alzheimer’s Disease over a period of 3 months. We showed that neurovascular responses were preserved compared to age matched wildtype controls. These results failed to confirm previous investigations reporting a marked reduction of neurovascular coupling in the J20-AD mouse model. However, when our procedure involved acute surgical procedures, previously reported neurovascular deficits were observed. The effects of acute electrode implantation were caused by disturbances to baseline physiology rather than a consequence of the disease condition. These results highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.
On estimating evolutionary probabilities of population variants
Authors: Patel Ravi , Kumar Sudhir 
Published: November 2018

AbstractBackgroundThe evolutionary probability (EP) of an allele in a DNA or protein sequence predicts evolutionarily permissible (ePerm; EP ≥ 0.05) and forbidden (eForb; EP < 0.05) variants. EP of an allele represents an independent evolutionary expectation of observing an allele in a population based solely on the long-term substitution patterns captured in a multiple sequence alignment. In the neutral theory, EP and population frequencies can be compared to identify neutral and non-neutral alleles. This approach has been used to discover candidate adaptive polymorphisms in humans, which are eForbs segregating with high frequencies. The original method to compute EP requires the evolutionary relationships and divergence times of species in the sequence alignment (a timetree), which are not known with certainty for most datasets. This requirement impedes a general use of the original EP formulation. Here, we present an approach in which the phylogeny and times are inferred from the sequence alignment itself prior to the EP calculation. We evaluate if the modified EP approach produces results that are similar to those from the original method.ResultsWe compared EP estimates from the original and the modified approaches by using more than 18,000 protein sequence alignments containing orthologous sequences from 46 vertebrate species. For the original EP calculations, we used species relationships from UCSC and divergence times from TimeTree web resource, and the resulting EP estimates were considered to be the ground truth. We found that the modified approaches produced reasonable EP estimates for HGMD disease missense variant and 1000 Genomes Project missense variant datasets. Our results showed that reliable estimates of EP can be obtained without a priori knowledge of the sequence phylogeny and divergence times. We also found that, in order to obtain robust EP estimates, it is important to assemble a dataset with many sequences, sampling from a diversity of species groups.ConclusionWe conclude that the modified EP approach will be generally applicable for alignments and enable the detection of potentially neutral, deleterious, and adaptive alleles in populations.
High-quality assembly of sweet basil genome
Authors: Dudai Nativ , Carp Marie-Jeanne , Milavski Renana , Chaimovitsh David , Shachter Alona , Baruch Kobi , Ronen Gil , Gonda Itay 
Published: November 2018

AbstractSweet basil, sometimes called the King of Herbs, is well known for its culinary uses, especially in the Italian sauce ‘Pesto’. It is also used in traditional medicine, as a source for essential oils and as an ornamental plant. So far, basil was bred by classical and traditional methods due to lack of a reference genome that will allow optimized application of the most up-to-date sequencing techniques. Here, we report on the first completion of the sweet basil genome of the cultivar ‘Perrie’, a fresh-cut Genovese-type basil, using several next generation sequencing platforms followed by genome assembly with NRGENE’s DeNovoMAGIC assembly tool. We determined that the genome size of sweet basil is 2.13 Gbp and assembled it into 12,212 scaffolds. The high-quality of the assembly is reflected in that more than 90% of the assembly size is composed of only 107 scaffolds. An independent analysis of single copy orthologues genes showed a 93% completeness which reveal also that 74% of them were duplicated, indicating that the sweet basil is a tetraploid organism. A reference genome of sweet basil will enable to develop precise molecular markers for various agricultural important traits such as disease resistance and tolerance to various environmental conditions. We will gain a better understanding of the underlying mechanisms of various metabolic processes such as aroma production and pigment accumulation. Finally, it will save time and money for basil breeders and scientists and ensure higher throughput and robustness in future studies.
Optimized fragmentation improves the identification of peptides cross-linked using MS-cleavable reagents
Authors: Stieger Christian E. , Doppler Philipp , Mechtler Karl 
Published: November 2018

ABSTRACTCross-linking mass spectrometry (XLMS) is becoming increasingly popular, and current advances are widening the applicability of the technique so that it can be utilized by non-specialist laboratories. Specifically, the use of novel mass spectrometry-cleavable (MS-cleavable) reagents dramatically reduces complexity of the data by providing i) characteristic reporter ions and ii) the mass of the individual peptides, rather than that of the cross-linked moiety. However, optimum acquisition strategies to obtain the best quality data for such cross-linkers with higher energy C-trap dissociation (HCD) alone is yet to be achieved. Therefore, we have carefully investigated and optimized MS parameters to facilitate the identification of disuccinimidyl sulfoxide (DSSO)- based cross-links on HCD-equipped mass spectrometers. From the comparison of 9 different fragmentation energies we chose several stepped-HCD fragmentation methods that were evaluated on a variety of cross-linked proteins. The optimal stepped-HCD-method was then directly compared with previously described methods using an Orbitrap Fusion™ Lumos™ TribridTM instrument using a high-complexity sample. The final results indicate that our stepped-HCD method is able to identify more cross-links than other methods, mitigating the need for multistage MS (MSn) enabled instrumentation and alternative dissociation techniques.
Time-resolved systems analysis reveals a critical role of XCR1+ dendritic cells in the maintenance of effector T cells during chronic viral infection
Authors: Argilaguet Jordi , Pedragosa Mireia , Esteve-Codina Anna , Riera Graciela , Vidal Enric , Peligero-Cruz Cristina , Andreu David , Kaisho Tsuneyasu , Bocharov Gennady , Ludewig Burkhard , Heath Simon , Meyerhans Andreas 
Published: November 2018

AbstractUpon a viral infection, the host immune system attempts to eradicate the virus. However, once the infection threat seems overwhelming, the infected host actively shuts down effector responses to reduce immunopathology. The price to pay for this is the establishment of a chronic infection that is only partially controlled by a lower level immune response. The genetic networks underlying this infection fate decision and the immune adaptation to the lower level response are not well understood. Here we used an integrated approach of gene coexpression network analysis of time-resolved splenic transcriptomes and immunological analysis to characterize the host response to acute and chronic lymphocytic choriomeningitis virus (LCMV) infections. We found first, an early attenuation of inflammatory monocyte/macrophage prior to the onset of T cell exhaustion and second, a critical role of the XCL1-XCR1 communication axis during the functional adaptation of the T cell response to the chronic infection state. These findings not only reveal an important feedback mechanism that couples T cell exhaustion with the maintenance of a lower level of effector T cell response but also suggest therapy options to better control virus levels during the chronic infection phase.Author SummaryThe outcomes of viral infections are the result of dynamic interplays between infecting viruses and induced host responses. They can be categorized as either acute or chronic depending on temporal virus-host relationships. Chronic infections are associated with immune exhaustion, a partial shut-down of effector responses. The processes underlying infection fate decisions are incompletely understood. Here we analyzed, on a systems level, infection-fate–specific gene signatures and the resulting adaptive processes of the host. We used the well-established lymphocytic choriomeningitis virus infection mouse model which has been instrumental to detect many fundamental processes in the virus-immune system crosstalk that are also relevant in human infections. We show an early attenuation of macrophage-mediated inflammation and an involvement of cross-presenting dendritic cells in the maintenance of an antiviral cytotoxic T cell response and virus control in the chronic infection phase. Together our data demonstrate a delicate adaptation process towards a chronic virus infection with both immunosuppressive and immunostimulatory processes. We fill a knowledge gap regarding the mechanisms of effector T cell maintenance and provide a new rational for targeted therapeutic vaccination.
The impact of bilateral ongoing activity on evoked responses in mouse cortex
Authors: Shimaoka Daisuke , Steinmetz Nicholas A , Harris Kenneth D , Carandini Matteo 
Published: November 2018

AbstractThe ongoing activity of the left and right cortical hemispheres shows strong bilateral fluctuations. Here we show that these fluctuations are largely responsible for the variability observed in cortical responses to sensory stimuli. Using widefield imaging of voltage and calcium signals, we measured activity in the cortex of mice performing a visual detection task. Bilateral fluctuations invested all areas, particularly those closest to the midline. Activity was less bilateral in the monocular region of primary visual cortex and, especially during task engagement, in secondary motor cortex. Ongoing bilateral fluctuations dominated unilateral visual responses, and interacted additively with them, explaining much of the variance in trial-by-trial activity. Even though these fluctuations occurred in regions necessary for the task, they did not impact detection behavior. We conclude that bilateral ongoing activity continues during sensory stimulation and has a powerful additive impact on sensory processing.
C. elegans pathogenic learning confers multigenerational pathogen avoidance
Authors: Moore Rebecca S. , Kaletsky Rachel , Murphy Coleen T. 
Published: November 2018

AbstractThe ability to pass on learned information to progeny could present an evolutionary advantage for many generations. While apparently evolutionarily conserved1–12, transgenerational epigenetic inheritance (TEI) is not well understood at the molecular or behavioral levels. Here we describe our discovery that C. elegans can pass on a learned pathogenic avoidance behavior to their progeny for several generations through epigenetic mechanisms. Although worms are initially attracted to the gram-negative bacteria P. aeruginosa (PA14)13, they can learn to avoid this pathogen13. We found that prolonged PA14 exposure results in transmission of avoidance behavior to progeny that have themselves never been exposed to PA14, and this behavior persists through the fourth generation. This form of transgenerational inheritance of bacterial avoidance is specific to pathogenic P. aeruginosa, requires physical contact and infection, and is distinct from CREB-dependent long-term associative memory and larval imprinting. The TGF-β ligand daf-7, whose expression increases in the ASJ upon initial exposure to PA1414, is highly expressed in the ASI neurons of progeny of trained mothers until the fourth generation, correlating with transgenerational avoidance behavior. Mutants of histone modifiers and small RNA mediators display defects in naïve PA14 attraction and aversive learning. By contrast, the germline-expressed PRG-1/Piwi homolog15 is specifically required for transgenerational inheritance of avoidance behavior. Our results demonstrate a novel and natural paradigm of TEI that may optimize progeny decisions and subsequent survival in the face of changing environmental conditions.
Attraction to pheromones inCaenorhabditis eleganscan be reversed through associative learning
Authors: Bello M. Dal , Pérez-Escudero A. , Schroeder F. C. , Gore J. 
Published: November 2018

AbstractDespite the ubiquity and importance of chemical signaling, we have only limited insight about the role of learning in the response to pheromones. Here, we demonstrate that responses to pheromones can be reprogrammed through associative learning. In particular, we show that attraction to ascaroside pheromones in the model nematodeCaenorhabditis eleganscan be reversed by training the animals to associate either a pheromone blend or single synthetic ascarosides with the lack of food. This behavioral plasticity alters worm preference for pheromones following consumption of a food patch, possibly improving foraging in natural environments. By bridging the gap between the current knowledge on the chemical language and the learning abilities ofC. elegans, we provide insight on the possible links between learning and chemical signaling in animals.
The sustained release of basic fibroblast growth factor accelerates angiogenesis and the survival of the inactivated dermis by high hydrostatic pressure
Authors: Le Tien Minh , Morimoto Naoki , Mitsui Toshihito , Notodihardjo Sharon Claudia , Munisso Maria Chiara , Kakudo Natsuko , Kusumoto Kenji 
Published: November 2018

AbstractWe developed a novel skin regeneration therapy combining nevus tissue inactivated by high hydrostatic pressure (HHP) in the reconstruction of the dermis with a cultured epidermal autograft (CEA). The issue with this treatment is the unstable survival of CEA on the inactivated dermis. In this study, we applied collagen/gelatin sponge (CGS), which can sustain the release of basic fibroblast growth factor (bFGF), to the inactivated skin in order to accelerate angiogenesis. Murine skin grafts from C57BL6J/Jcl mice (8 mm in diameter) were prepared, inactivated by HHP and cryopreserved. One month later, the grafts were transplanted subcutaneously onto the back of other mice and covered by CGS impregnated with saline or bFGF. Grafts were taken after one, two and eight weeks, at which point the survival was evaluated through the histology and angiogenesis-related gene expressions were determined by real-time polymerase chain reaction. Histological sections showed that the dermal cellular density and newly formed capillaries in the bFGF group were significantly higher than in the control group. The relative expression of FGF-2, PDGF-A and VEGF-A genes in the bFGF group was significantly higher than in the control group at Week 1. This study suggested that the angiogenesis into grafts was accelerated, which might improve the survival in combination with the sustained release of bFGF by CGSs.