bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis uncovers mechanisms of plasticity in leukemia initiating cells
Authors: Morris Vivian , Marion William , Hughes Travis , Sousa Patricia , Sensharma Prerana , Pikman Yana , Harris Marian , Shalek Alex K. , North Trista E. , Daley George Q. , da Rocha Edroaldo Lummertz , Rowe R. Grant 
Published: May 2020

ABSTRACTLeukemia initiating cells (LICs) fuel leukemic growth and spark relapse. Previously thought to be primitive and rare, the LIC state may actually be heterogeneous and dynamic, enabling evasion of therapies. Here, we use single-cell transcriptomics to track LIC multipotency within the cellular ontogeny ofMLL-rearranged B-lymphoblastic leukemia (MLL-r B-ALL). Although we identify rare transcriptionally and phenotypically primitive LICs, we also observe LICs emerging from more differentiated populations with the capability to replenish the full leukemic cellular diversity. We find that activation of MYC-driven oxidative phosphorylation controls this process of facultative state conversion in LICs.
The habenula clock influences prediction of danger
Authors: Basnakova Adriana , Cheng Ruey-Kuang , Ming Joanne Chia Shu , D’Agostino Giuseppe , Suryadi  , Hui Germaine Tan Jia , Langley Sarah R. , Jesuthasan Suresh 
Published: May 2020

AbstractThe response of an animal to a sensory stimulus depends on the nature of the stimulus and on predictions mediated by spontaneous activity in neurons. Here, we ask how circadian variation in the prediction of danger, and thus the response to a potential threat, is controlled. We focus on the habenula, a mediator of threat response that functions by regulating neuromodulator release, and use zebrafish as the experimental system. Single cell transcriptomics indicates that multiple clock genes are expressed throughout the habenula, while quantitative in situ hybridization confirms that the clock oscillates. Two-photon calcium imaging indicates a circadian change in spontaneous activity of habenula neurons. To assess the role of this clock, a truncated clocka gene was specifically expressed in the habenula. This partially inhibited the clock, as shown by changes in per3 expression as well as altered day-night variation in dopamine, serotonin and acetylcholine levels. Behaviourally, anxiety-like responses evoked by an alarm pheromone were reduced. Circadian effects of the pheromone were disrupted, such that responses in the day resembled those at night. Behaviours that are regulated by the pineal clock and not triggered by stressors were unaffected. These findings establish that the habenula clock regulates the expectation of danger, thus identifying one mechanism for circadian change in the response to a stressor.
Bioinformatic and experimental evidence for suicidal and catalytic plant THI4s
Authors: Joshi Jaya , Beaudoin Guillaume A.W. , Patterson Jenelle A. , García-García Jorge D. , Belisle Catherine E. , Chang Lan-Yen , Li Lei , Duncan Owen , Millar A. Harvey , Hanson Andrew D. 
Published: May 2020

ABSTRACTLike fungi and some prokaryotes, plants use a thiazole synthase (THI4) to make the thiazole precursor of thiamin. Fungal THI4s are suicide enzymes that destroy an essential active-site Cys residue to obtain the sulfur atom needed for thiazole formation. In contrast, certain prokaryotic THI4s have no active-site Cys, use sulfide as sulfur donor, and are truly catalytic. The presence of a conserved active-site Cys in plant THI4s and other indirect evidence implies that they are suicidal. To confirm this, we complemented the Arabidopsistz-1mutant, which lacks THI4 activity, with a His-tagged Arabidopsis THI4 construct. LC-MS analysis of tryptic peptides of the THI4 extracted from leaves showed that the active-site Cys was predominantly in desulfurated form, consistent with THI4 having a suicide mech-anismin planta. Unexpectedly, transcriptome datamining and deep proteome profiling showed that barley, wheat, and oat have both a widely expressed canonical THI4 with an active-site Cys, and a THI4-like paralog (non-Cys THI4) that has no active-site Cys and is the major type of THI4 in devel-oping grains. Transcriptomic evidence also indicated that barley, wheat, and oat grains synthesize thiaminde novo, implying that their non-Cys THI4s synthesize thiazole. Structure modeling supported this inference, as did demonstration that non-Cys THI4s have significant capacity to complement thia-zole auxotrophy inEscherichia coli. There is thus aprima faciecase that non-Cys cereal THI4s, like their prokaryotic counterparts, are catalytic thiazole synthases. Bioenergetic calculations show that, relative to suicide THI4s, such enzymes could save substantial energy during the grain filling period.AbbreviationsDHAla, dehydroalanine; EST, expressed sequence tag; FDR, false discovery rate; IPTG, β-D-1-thiogalactopyranoside
Why species richness of plants and herbivorous insects do or do not correlate
Authors: Shinohara Naoto , Yoshida Takehito 
Published: May 2020

AbstractUnraveling the determinants of herbivorous insect diversity has been a major challenge in ecology. Despite the strong association between insect and plant species, previous studies conducted in natural systems have shown great variation in the strength of the correlation between their species richness. Such variation can be attributed to the proportion of generalist insect species (generality), though both higher and lower generality may weaken the correlation because 1) generalist insect species are less dependent on the number of plant species and 2) specialist insect species utilize only a part of the total plant species. To explore these opposing effects, we studied plant and herbivorous insect communities in semi-natural grasslands in Japan. Plant–insect interactions were evaluated in a unique way with a particular focus on the staying and herbivory behaviors of insects, which reflect their habitat use as well as host use. We fousnd that generality of insect communities negatively affected the correlation between species richness of plants and insects. However, such negative effect was significant only when the insect species richness was related with the number of plant species interacted with some insect species, instead of with that of total plant species. The results suggest that considering either of the opposing effects of insect generality is insufficient and they should be inclusively interpreted to understand the relationship between plant and insect species richness.
PCNA has specific functions in regulation of metabolism in haematological cells
Authors: Røst Lisa M. , Olaisen Camilla , Sharma Animesh , Nedal Aina , Petrovic Voin , Kvitvang Hans Fredrik N. , Bruheim Per , Otterlei Marit 
Published: May 2020

AbstractPCNA’s essential roles in DNA replication and repair are well established, while its recently discovered cytosolic roles are less explored. Here we show that impairing PCNA’s cytosolic scaffold functions led to massive changes in cellular signaling, and most strikingly, a strong reduction in glycolytic metabolite and nucleoside phosphate pools in haematological cancer cells. This was not detected in cells from solid tissues nor in primary monocytes from healthy donors. However, lipopolysaccharide stimulated monocytes responded to targeting PCNA’s scaffold function similarly to haematological cancer cells, suggesting that cellular stress is an important factor for the observed response. Integrated transcriptome, proteome and metabolome analysis revealed that pathways involved in protein stability/folding and immune responses were affected in haematopoietic cancer cells. Altogether, our data suggests that PCNA has an important role in regulation of cytoplasmic stress via regulation of central carbon metabolism in haematological cells, which potentially can be targeted in cancer treatment.HighlightA strong reduction in glycolytic metabolites and the nucleoside phosphate pools was detected in haematological cancer cells upon inhibiting PCNA scaffold functions. These metabolic changes were not found in cancer cells from other tissues, indicating a special role of PCNA in regulation of metabolism in cells of haematological origin.
Does hippocampal volume explain performance differences on hippocampal-dependent tasks?
Authors: Clark Ian A. , Monk Anna M. , Hotchin Victoria , Pizzamiglio Gloria , Liefgreen Alice , Callaghan Martina F. , Maguire Eleanor A. 
Published: May 2020

AbstractMarked disparities exist across healthy individuals in their ability to imagine scenes, recall autobiographical memories, think about the future and navigate in the world. The importance of the hippocampus in supporting these critical cognitive functions has prompted the question of whether differences in hippocampal grey matter volume could be one source of performance variability. Evidence to date has been somewhat mixed. In this study we sought to mitigate issues that commonly affect these types of studies. Data were collected from a large sample of 217 young, healthy adult participants, including whole brain structural MRI data (0.8mm isotropic voxels) and widely-varying performance on scene imagination, autobiographical memory, future thinking and navigation tasks. We found little evidence that hippocampal grey matter volume was related to task performance in this healthy sample. This was the case using different analysis methods (voxel-based morphometry, partial correlations), when whole brain or hippocampal regions of interest were examined, when comparing different sub-groups (divided by gender, task performance, self-reported ability), and when using latent variables derived from across the cognitive tasks. Hippocampal grey matter volume may not, therefore, significantly influence performance on tasks known to require the hippocampus in healthy people. Perhaps only in extreme situations, as in the case of licensed London taxi drivers, are measurable ability-related hippocampus volume changes consistently exhibited.HighlightsEvidence is mixed about whether hippocampal volume affects cognitive task performanceThis is particularly the case concerning individual differences in healthy peopleWe collected structural MRI data from 217 healthy peopleThey also had widely-varying performance on cognitive tasks linked to the hippocampusIn-depth analyses showed little evidence hippocampal volume affected task performance
Nano-analytical Characterization of Breast Tissue Biopsies Reveals an Association between Spherical Nano and Micro Particles and Invasive Malignant Breast Tumours
Authors: Tsolaki Elena , Doran William , Overbeck Jan , Magnani Luca , Olivo Alessandro , Herrmann Inge K. , Bertazzo Sergio 
Published: May 2020

SummaryThe presence of calcifications on mammograms is a widely used diagnostic marker for breast cancer. While the clinicopathological analysis of breast tissue is well-developed, an in-depth characterisation of the properties of calcifications at the micro and nano scale remained elusive. In this work, we use nano-analytical methods to investigate the calcification present in healthy breast tissue, as well as in benign and malignant breast tumour tissue biopsies. While polycrystalline apatite with lower crystallinity can be found in all breast tissue samples, we show that magnesium-containing nano and micro spherical particles are found only in malignant invasive breast cancers. These particles concentration increases with cancer progression. The discovery of these spherical particles provides new insights into the characteristics of breast calcification associated with malignant tumours and opens new research pathways to a better understanding of breast tumours and their microenvironment in general.
Cortical and subcortical hemodynamic changes during human sleep slow waves
Authors: Betta Monica , Handjaras Giacomo , Leo Andrea , Federici Alessandra , Farinelli Valentina , Ricciardi Emiliano , Siclari Francesca , Meletti Stefano , Ballotta Daniela , Benuzzi Francesca , Bernardi Giulio 
Published: May 2020

AbstractEEG slow waves, the hallmarks of NREM sleep, are closely linked to the restorative function of sleep and their regional cortical distribution reflects plasticity- and learning-related processes. Here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to sleep slow waves. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were found in several areas, including insula and somatomotor cortex, and were preceded by slow signal increases that peaked around slow-wave onset. EEG slow waves and BOLD fluctuations showed similar cortical propagation patterns, from centro-frontal to temporo-occipital cortices. These regional patterns of hemodynamic-electrical coupling are consistent with theoretical accounts of the functions of sleep slow waves.
Is a long hygroscopic awn an advantage forThemeda triandrain drier areas?
Authors: Morris Craig D 
Published: May 2020

AbstractThemeda triandrahas bigeniculate hygroscopic lemma seed awns that twist when wet and drying, thereby transporting the caryopsis across the soil surface into suitable germination microsites. The prediction that awns would be longer in drier grassland and have greater motility to enable them to move quickly and further to find scarce germination sites was tested in KwaZulu-Natal. Awns (n = 100) were collected from 16 sites across a mean annual precipitation gradient (575-1223 mm), ranging from 271-2097 m a.s.l. The daily movement of hydrated long and short awns (n = 10) across blotting paper was tracked for five days, and the rotational speed of anchored awns was measured. Awn length varied considerably (mean: 41.4-63.2 mm; sd: 3.44-8.99) but tended to increase (r = 0.426, p = 0.099) not decline, with increasing MAP. Awn length was unrelated to elevation, temperature and aridity indices. Long awns rotated at the same rate (2 min 48 sec) but moved twice as fast (46.3 vs. 22.1 mm day-1) and much further (maximum: 82.1 vs. 38.6 mm day-1) than short awns. Whether moisture limits awn development, the benefit of longer awns to negotiate densely tufted mesic grassland, and the multifunctionality of awns require investigation.
Common datastream permutations of animal social network data are not appropriate for hypothesis testing using regression models
Authors: Weiss Michael N. , Franks Daniel W. , Brent Lauren J. N. , Ellis Samuel , Silk Matthew J. , Croft Darren P. 
Published: May 2020

AbstractSocial network methods have become a key tool for describing, modelling, and testing hypotheses about the social structures of animals. However, due to the non-independence of network data and the presence of confounds, specialized statistical techniques are often needed to test hypotheses in these networks. Datastream permutations, originally developed to test the null hypothesis of random social structure, have become a popular tool for testing a wide array of null hypotheses. In particular, they have been used to test whether exogenous factors are related to network structure by interfacing these permutations with regression models.Here, we show that these datastream permutations typically do not represent the null hypothesis of interest to researchers interfacing animal social network analysis with regression modelling, and use simulations to demonstrate the potential pitfalls of using this methodology.Our simulations show that utilizing common datastream permutations to test the coefficients of regression models can lead to extremely high type I (false-positive) error rates (> 30%) in the presence of non-random social structure. The magnitude of this problem is primarily dependent on the degree of non-randomness within the social structure and the intensity of samplingWe strongly recommend against utilizing datastream permutations to test regression models in animal social networks. We suggest that a potential solution may be found in regarding the problems of non-independence of network data and unreliability of observations as separate problems with distinct solutions.
New Music System Reveals Spectral Contribution to Statistical Learning
Authors: Loui Psyche 
Published: May 2020

1AbstractKnowledge of speech and music depends upon the ability to perceive relationships between sounds in order to form a stable mental representation of statistical structure. Although evidence exists for the learning of musical scale structure from the statistical properties of sound events, little research has been able to observe how specific acoustic features contribute to statistical learning independent of the effects of long-term exposure. Here, using a new musical system, we show that spectral content is an important cue for acquiring musical scale structure. In two experiments, participants completed probe-tone ratings before and after a half-hour period of exposure to melodies in a novel musical scale with a predefined statistical structure. In Experiment 1, participants were randomly assigned to either a no-exposure control group, or to exposure groups who heard pure tone or complex tone sequences. In Experiment 2, participants were randomly assigned to exposure groups who heard complex tones constructed with odd harmonics or even harmonics. Learning outcome was assessed by correlating pre/post-exposure ratings and the statistical structure of tones within the exposure period. Spectral information significantly affected sensitivity to statistical structure: participants were able to learn after exposure to all tested timbres, but did best at learning with timbres with odd harmonics, which were congruent with scale structure. Results show that spectral amplitude distribution is a useful cue for statistical learning, and suggest that musical scale structure might be acquired through exposure to spectral distribution in sounds.
Continuous Reports of Sensed Hand Position During Sensorimotor Adaptation
Authors: Tsay Jonathan S. , Parvin Darius E. , Ivry Richard B. 
Published: May 2020

ABSTRACTSensorimotor learning entails multiple learning processes, some volitional and explicit, and others automatic and implicit. A new method to isolate implicit adaptation involves the use of a “clamped” visual perturbation in which, during a reaching movement, visual feedback is limited to a cursor that follows an invariant trajectory, offset from the target by a fixed angle. Despite full awareness that the cursor movement is not contingent on their behavior, as well as explicit instructions to ignore the cursor, systematic changes in motor behavior are observed, and these changes have the signatures of implicit adaptation observed in studies using classic visuomotor perturbations. While it is clear that the response to clamped feedback occurs automatically, it remains unknown if the adjustments in behavior remain outside the participant’s awareness. To address this question, we used the clamp method and directly probed awareness by asking participants to report their hand position after each reach. As expected, we observed robust deviations in hand angle away from the target (average of ∼18°). The hand reports also showed systematic deviations over the course of adaptation, initially attracted towards the visual feedback and then in the opposite direction, paralleling the shift in hand position. However, these effects were subtle (∼2° at asymptote), with the hand reports dominated by a feedforward signal associated with the motor intent yet modulated in a limited way by feedback sources. These results confirm that adaptation in response to a visual perturbation is not only automatic, but also largely implicit.NEWS AND NOTEWORTHYSensorimotor adaptation operates in an obligatory manner. Qualitatively, subjective reports obtained after adaptation demonstrate that, in many conditions, participants are unaware of significant changes in behavior. In the present study, we quantified participants’ awareness of adaptation by obtaining reports of hand position on a trial-by-trial basis. The results confirm that participants are largely unaware of adaptation, but also reveal the subtle influence of feedback on their subjective experience.
How repeated outbreaks drive the evolution of bacteriophage communication: Insights from a mathematical model
Authors: Doekes Hilje M. , Mulder Glenn A. , Hermsen Rutger 
Published: May 2020

AbstractCommunication based on small signalling molecules is widespread among bacteria. Recently, such communication was also described in bacteriophages. Upon infection of a host cell, temperate phages of theBacillus subtilis-infecting SPbeta group induce the secretion of a phage-encoded signalling peptide, which is used to inform the lysis-lysogeny decision in subsequent infections: the phages produce new virions and lyse their host cell when the signal concentration is low, but favour a latent infection strategy, lysogenising the host cell, when the signal concentration is high. Here, we present a mathematical model to study the ecological and evolutionary dynamics of such viral communication. We show that a communication strategy in which phages use the lytic cycle early in an outbreak (when susceptible host cells are abundant) but switch to the lysogenic cycle later (when susceptible cells become scarce) is favoured over a bet-hedging strategy in which cells are lysogenised with constant probability. However, such phage communication can evolve only if phage-bacteria populations are regularly perturbed away from their equilibrium state, so that acute outbreaks of phage infections in pools of susceptible cells continue to occur. Our model then predicts the selection of phages that switch infection strategy when half of the available susceptible cells have been infected.
FromATOMtoGradiATOM: Cortical gradients support time and space processing as revealed by a meta-analysis of neuroimaging studies
Authors: Cona Giorgia , Wiener Martin , Scarpazza Cristina 
Published: May 2020

AbstractAccording to the ATOM (A Theory Of Magnitude), formulated by Walsh more than fifteen years ago, there is a general system of magnitude in the brain that comprises regions, such as the parietal cortex, shared by space, time and other magnitudes (Walsh, 2003).The present meta-analysis of neuroimaging studies used the Activation Likelihood Estimation (ALE) method in order to determine the set of regions commonly activated in space and time processing and to establish the neural activations specific to each magnitude domain. Following PRISMA guidelines, we included in the analysis a total of 112 and 114 experiments, exploring space and time processing, respectively.We clearly identified the presence of a system of brain regions commonly recruited in both space and time and that includes: bilateral insula, the pre-supplementary motor area (SMA), the right frontal operculum and the intraparietal sulci. These regions might be the best candidates to form the core magnitude neural system. Surprisingly, along each of these regions but the insula, ALE values progressed in a cortical gradient from time to space. The SMA exhibited an anterior-posterior gradient, with space activating more-anterior regions (i.e., pre-SMA) and time activating more-posterior regions (i.e., SMA-proper). Frontal and parietal regions showed a dorsal-ventral gradient: space is mediated by dorsal frontal and parietal regions, and time recruits ventral frontal and parietal regions.Our study supports but also expands the ATOM theory. Therefore, we here re-named it the ‘GradiATOM’ theory (Gradient Theory of Magnitude), proposing that gradient organization can facilitate the transformations and integrations of magnitude representations by allowing space- and time-related neural populations to interact with each other over minimal distances.