bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential repression of Otx2 underlies the capacity of NANOG and ESRRB to induce germline entry
Authors: Vojtek Matúš , Zhang Jingchao , Sun Juanjuan , Zhang Man , Chambers Ian 
Published: June 2021

SummaryPrimordial germ cells (PGCs) are induced in the embryo by signals, including BMP emanating from extra-embryonic ectoderm, that act on cells in the post-implantation epiblast. PGC development can be recapitulated in vitro through the exposure of epiblast-like cells (EpiLCs) to appropriate cytokines, resulting in differentiation into PGC-like cells (PGCLCs). Interestingly, the requirement for cytokines to induce PGCLCs can be bypassed by enforced expression of the transcription factor (TF) NANOG. However, the underlying mechanisms are not fully elucidated. Here, we show that Otx2 downregulation is essential to enable NANOG to induce PGCLC formation. Moreover, while previous work has shown that the direct NANOG target gene Esrrb can substitute for several functions of NANOG, enforced expression of ESRRB cannot promote PGCLC specification from EpiLCs. This appears to be due to differential downregulation of Otx2 by NANOG and ESRRB, since induction of ESRRB in Otx2+/- EpiLCs activates expression of the core PGC TFs, Blimp1, Prdm14 and Ap2γ and emergence of PGCLCs. This study illuminates the interplay of TFs occurring at the earliest stages of PGC specification from a state of competence.
X-ray induced bio-acoustic emissions from cultured cells
Authors: Matarèse Bruno F.E. , Rahmoune Hassan , Vo Nguyen T. K. , Seymour Colin B. , Schofield Paul N. , Mothersill Carmel 
Published: June 2021

PurposeWe characterise for the first time the emission of bio-acoustic waves from cultured cells irradiated at doses of X-ray photon radiation relevant to medical and accidental exposure.Methods and materialsHuman cancer cell lines (MCF-7, HL-60) and control cell-free media were exposed to 1 Gy X-ray photons while recording the sound generated before, during and after irradiation. Cellular cytotoxicity following photon irradiation was determined by extracellular LDH levels, and irradiated cell conditioned media were tested for their ability to elicit a bystander effect in reporter cells.ResultsWe report the first recorded acoustic signals captured from a collective pressure wave response to ionising irradiation. The signature of the collective acoustic peaks was temporally wider and with higher acoustic power for irradiated HL-60 than for irradiated MCF-7.ConclusionsWe show that at doses of X-ray irradiation capable of producing the release of bystander effect-inducing activity, both cell types emit a characteristic acoustic signal for the duration of the radiation pulse. The rapid signal decay is consistent with a passive rather than an active acoustic signal generation. This preliminary study suggests that further work on the potential role of radiation induced acoustic emission (RIAE) in the cellular bystander effect is merited.
Managing African Swine Fever: Assessing the Potential of Camera Traps in Monitoring Wild Boar Occupancy Trends in Infected and Noninfected Zones, Using Spatio-temporal Statistical Models
Authors: Bollen Martijn , Neyens Thomas , Fajgenblat Maxime , De Waele Valérie , Licoppe Alain , Manet Benoît , Casaer Jim , Beenaerts Natalie 
Published: June 2021

AbstractThe recent spreading of African swine fever (ASF) over the Eurasian continent has been acknowledged as a serious economic threat for the pork industry. Consequently, an extensive body of research focuses on the epidemiology and control of ASF. Nevertheless, little information is available on the combined effect of ASF and ASF-related control measures on wild boar (Sus scrofa) population abundances. This is crucial information given the role of the remaining wild boar that act as an important reservoir of the disease. Given the high potential of camera traps as a non-invasive method for ungulate trend estimation, we assess the effectiveness of ASF control measures using a camera trap network. In this study, we focus on a major ASF outbreak in 2018-2020 in the South of Belgium. This outbreak elicited a strong management response, both in terms of fencing off a large infected zone as well as an intensive culling regime. We apply a Bayesian multi-season site-occupancy model to wild boar detection-nondetection data. Our results show that (1) occupancy rates at the onset of our monitoring period reflect the ASF infection status; (2) ASF-induced mortality and culling efforts jointly lead to decreased occupancy over time; and (3) the estimated mean total extinction rate ranges between 22.44% and 91.35%, depending on the ASF infection status. Together, these results confirm the effectiveness of ASF-control measures implemented in Wallonia (Belgium), which has regained its disease-free status in December 2020, as well as the usefulness of a camera trap network to monitor these effects.
Longitudinal Developmental Trajectories Do Not Follow Cross-Sectional Age Associations in Hippocampal Subfield and Memory Development
Authors: Keresztes Attila , Raffington Laurel , Bender Andrew R. , Bögl Katharina , Heim Christine , Shing Yee Lee 
Published: June 2021

AbstractMany cross-sectional findings suggest that volumes of specific hippocampal subfields increase in middle childhood and early adolescence. In contrast, a small number of available longitudinal studies observed decreased volumes in most subfields over this age range. Further, it remains unknown whether structural changes in development are associated with corresponding gains in children’s memory. Here we report cross-sectional age differences in children’s hippocampal subfield volumes together with longitudinal developmental trajectories and their relationships with memory performance. In two waves, 109 healthy participants aged 6 to 10 years (wave 1: MAge=7.25, wave 2: MAge=9.27) underwent high-resolution magnetic resonance imaging to assess hippocampal subfield volumes, and completed cognitive tasks assessing hippocampus dependent memory processes. We found that cross-sectional age-associations and longitudinal developmental trends in hippocampal subfield volumes were highly discrepant, both by subfields and in direction. Further, volumetric changes were largely unrelated to changes in memory, with the exception that increase in subiculum volume was associated with gains in spatial memory. Importantly, the observed longitudinal patterns of brain-cognition coupling could not be inferred from cross-sectional findings. We discuss potential sources of these discrepancies. This study underscores that children’s structural brain development and its relationship to cognition cannot be inferred from cross-sectional age comparisons.HighlightsThe subiculum undergoes volumetric increase between 6-10 years of ageChange across two years in CA1-2 and DG-CA3 was not observed in this age windowChange across two years did not reflect age differences spanning two yearsCross-sectional and longitudinal slopes in stark contrast for hippocampal subfieldsLongitudinal brain-cognition coupling cannot be inferred from cross-sectional data
A novel and accurate full-length HTT mouse model for Huntington’s disease
Authors: Shenoy Sushila A , Zheng Sushuang , Liu Wencheng , Dai Yuanyi , Liu Yuanxiu , Hou Zhipeng , Mori Susumu , Duan Wenzhen , Li Chenjian 
Published: June 2021

AbstractHere we report the generation and characterization of a novel Huntington’s disease (HD) mouse model BAC226Q by using a bacterial artificial chromosome (BAC) system, expressing full-length human HTT with ∼226 CAG-CAA repeats and containing endogenous human HTT promoter and regulatory elements. BAC226Q recapitulated a full-spectrum of age-dependent and progressive HD-like phenotypes without unwanted and erroneous phenotypes. BAC226Q mice developed normally, and gradually exhibited HD-like mood and cognitive phenotypes at 2 months. From 3-4 months, BAC226Q mice showed robust progressive motor deficits. At 11 months, BAC226Q mice showed significant reduced life span, gradual weight loss and exhibit neuropathology including significant brain atrophy specific to striatum and cortex, striatal neuronal death, widespread huntingtin inclusions and reactive pathology. Therefore, the novel BAC226Q mouse accurately recapitulating robust, age-dependent, progressive HD-like phenotypes will be a valuable tool for studying disease mechanisms, identifying biomarkers and testing gene-targeting therapeutic approaches for HD.
Reconstitution of the DTX3L-PARP9 complex reveals determinants for high affinity heterodimer formation and enzymatic function
Authors: Ashok Yashwanth , Vela-Rodriguez Carlos , Yang Chunsong , Alanen Heli I. , Liu Fan , Paschal Bryce M. , Lehtiö Lari 
Published: June 2021

AbstractUbiquitination and ADP-ribosylation are post-translational modifications that play major roles in pathways like DNA damage response and infection, making them attractive targets for therapeutic intervention. DTX3L, an E3 ubiquitin ligase, forms a heterodimer with PARP9. The complex has ubiquitin ligase activity and also ADP-ribosylates the C-terminus of ubiquitin on Gly76. NAD+-dependent ADP-ribosylation of ubiquitin by DTX3L-PARP9 prevents ubiquitin from conjugating to protein substrates. By using individually produced proteins, we have studied the interaction between DTX3L and PARP9. We identify that the D3 domain (230 – 510) of DTX3L mediates interaction with PARP9 with nanomolar affinity and an apparent 1:1 stoichiometry. Our results also suggest the formation of a higher molecular weight oligomer mediated by the N-terminus of DTX3L (1-200). Furthermore, we show that ADP-ribosylation of ubiquitin at Gly76 is a reversible modification that can be removed by several macrodomain-type hydrolases. Our study provides a framework to understand how DTX3L-PARP9 mediates ADP-ribosylation and ubiquitination in an inter-regulatory manner.
Embryonic development of fully biocompatible organic light-emitting diodes
Authors: Matarèse Bruno F.E. 
Published: June 2021

AbstractPrototype fully biocompatible organic light-emitting diodes are investigated, with a view to creating a suitable and high-performance light source as a medical implant device. A selection of organic LED materials that have potential suitability for the biological environment are examined. First, the biocompatibility of selected OLED materials was evaluated by the study of cell adhesion and cytotoxicity of HeLa cells cultured on the candidate materials. Thus it was possible to design a device structure composed entirely of biocompatible materials. Second, the characterization of the electroluminescence properties of the prototype OLED is shown and its limitation evaluated. Third, the aqueous stability of the fully biocompatible light source is examined. There is strong evidence that fully biocompatible and stable light-emitting implant devices can be easily constructed. This is the first time a fully biocompatible organic light-emitting diode, albeit embryonic, is reported, with the hope that it may lead to further research to optimize the device performance. Some suggestions on suitable device properties towards in vivo transition are provided.
Cross-species metabolomic analysis of DDT and Alzheimer’s disease-associated tau toxicity
Authors: Kalia Vrinda , Niedzwiecki Megan M. , Bradner Joshua M. , Lau Fion K. , Bucher Meghan L. , Manz Katherine E. , Fuentes Zoe Coates , Pennell Kurt D. , Picard Martin , Walker Douglas I. , Hu William T. , Jones Dean P. , Miller Gary W. 
Published: June 2021

AbstractBackgroundThe formation of hyperphosphorylated tau (p-tau) protein tangles in neurons is a pathological marker of Alzheimer’s disease (AD). Exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) has been associated with increased risk of AD.ObjectivesTo determine if there was a connection between DDT exposure and tau toxicity we investigated whether exposure to DDT can exacerbate tau protein toxicity in C. elegans. In addition, we examined the association between p-tau protein and metabolism in a human population study and in a transgenic C. elegans strain neuronally expressing a mutant tau protein fragment that is prone to aggregation.MethodsIn the human population study, we used a metabolome-wide association framework to determine the association between p-tau measured in the cerebrospinal fluid (CSF) and metabolomic features measured in both plasma (n = 142) and CSF (n = 78) using high-resolution metabolomics (HRM). Using the same HRM method, we determined changes in metabolomic features in the transgenic C. elegans strain compared to its control strain. Metabolites associated with p-tau in both species were analyzed for overlap. We also examined the effect of DDT and aggregating tau protein on growth, swim behavior, mitochondrial function, metabolism, learning, and lifespan in C. elegans.ResultsPlasma and CSF-derived features associated with p-tau level were related to drug, amino acid, fatty acid and mitochondrial metabolism pathways. Five metabolites overlapped between plasma and C. elegans, and 4 between CSF and C. elegans. DDT exacerbated the inhibitory effect of aggregating tau protein on growth and basal respiration. In the presence of aggregating tau protein, DDT induced more curling and was associated with reduced levels of amino acids but increased levels of uric acid and adenosylselenohomocysteine. Developmental exposure to DDT blunted the lifespan reduction caused by aggregating tau protein.ConclusionThe model organism C. elegans can complement human studies by providing a means to study mechanisms of environmental toxicants. Specifically, our C. elegans data show that DDT exposure and tau protein aggregation both inhibit mitochondrial function and DDT exposure can exacerbate the mitochondrial inhibitory effects of tau protein aggregation providing a plausible explanation for the observed human associations.
The voltage and spiking responses of subthreshold resonant neurons to structured and fluctuating inputs: persistence and loss of resonance and variability
Authors: Pena Rodrigo F. O. , Rotstein Horacio G. 
Published: June 2021

AbstractWe systematically investigate the response of neurons to oscillatory currents and synaptic-like inputs and we extend our investigation to non-structured synaptic-like spiking inputs with more realistic distributions of presynaptic spike times. We use two types of chirp-like inputs consisting of (i) a sequence of cycles with discretely increasing frequencies over time, and (ii) a sequence having the same cycles arranged in an arbitrary order. We develop and use a number of frequency-dependent voltage response metrics to capture the different aspects of the voltage response, including the standard impedance (Z) and the peak-to-trough amplitude envelope (VENV) profiles. We show that Z-resonant cells (cells that exhibit subthreshold resonance in response to sinusoidal inputs) also show VENV-resonance in response to sinusoidal inputs, but generally do not (or do it very mildly) in response to square-wave and synaptic-like inputs. In the latter cases the resonant response using Z is not predictive of the preferred frequencies at which the neurons spike when the input amplitude is increased above subthreshold levels. We also show that responses to conductance-based synaptic-like inputs are attenuated as compared to the response to current-based synaptic-like inputs, thus providing an explanation to previous experimental results. These response patterns were strongly dependent on the intrinsic properties of the participating neurons, in particular whether the unperturbed Z-resonant cells had a stable node or a focus. In addition, we show that variability emerges in response to chirp-like inputs with arbitrarily ordered patterns where all signals (trials) in a given protocol have the same frequency content and the only source of uncertainty is the subset of all possible permutations of cycles chosen for a given protocol. This variability is the result of the multiple different ways in which the autonomous transient dynamics is activated across cycles in each signal (different cycle orderings) and across trials. We extend our results to include high-rate Poisson distributed current- and conductance-based synaptic inputs and compare them with similar results using additive Gaussian white noise. We show that the responses to both Poisson-distributed synaptic inputs are attenuated with respect to the responses to Gaussian white noise. For cells that exhibit oscillatory responses to Gaussian white noise (band-pass filters), the response to conductance-based synaptic inputs are low-pass filters, while the response to current-based synaptic inputs may remain band-pass filters, consistent with experimental findings. Our results shed light on the mechanisms of communication of oscillatory activity among neurons in a network via subthreshold oscillations and resonance and the generation of network resonance.
Marginally compact phase and ordered ground states in a model polymer with side spheres
Authors: Škrbić Tatjana , Hoang Trinh Xuan , Giacometti Achille , Maritan Amos , Banavar Jayanth R. 
Published: June 2021

AbstractWe present the results of a quantitative study of the phase behavior of a model polymer chain with side spheres using two independent computer simulation techniques. We find that the mere addition of side spheres results in key modifications of standard polymer behavior. One obtains a novel marginally compact phase at low temperatures, the structures in this phase are reduced in dimensionality and are ordered, they include strands assembled into sheets and a variety of helices, and at least one of the transitions on lowering the temperature to access these ordered states is found to be first order. Our model serves to partially bridge conventional polymer phases with biomolecular phases.
Multi-echo Quantitative Susceptibility Mapping: How to Combine Echoes for Accuracy and Precision at 3 T
Authors: Biondetti Emma , Karsa Anita , Grussu Francesco , Battiston Marco , Yiannakas Marios C. , Thomas David L. , Shmueli Karin 
Published: June 2021

AbstractPurposeTo compare different multi-echo combination methods for MRI quantitative susceptibility mapping (QSM). Given the current lack of consensus, we aimed to elucidate how to optimally combine multi-echo gradient-recalled echo (GRE) signal phase information, either before or after applying Laplacian-base methods (LBMs) for phase unwrapping or background field removal.MethodsMulti-echo GRE data were simulated in a numerical head phantom, and multiecho GRE images were acquired at 3 T in ten healthy volunteers. To enable image-based estimation of GRE signal noise, five volunteers were scanned twice in the same session without repositioning. Five QSM processing pipelines were designed: one applied nonlinear phase fitting over echo times (TEs) before LBMs; two applied LBMs to the TE-dependent phase and then combined multiple TEs via either TE-weighted or signal-to-noise ratio (SNR)-weighted averaging; two calculated TE-dependent susceptibility maps via either multi-step or single-step QSM and then combined multiple TEs via magnitude-weighted averaging. Results from different pipelines were compared using visual inspection; summary statistics of susceptibility in deep gray matter, white matter, and venous regions; phase noise maps (error propagation theory); and, in the healthy volunteers, regional fixed bias analysis (Bland-Altman) and regional differences between the means (nonparametric tests).ResultsNonlinearly fitting the multi-echo phase over TEs before applying LBMs provided the highest regional accuracy of χ and the lowest phase noise propagation compared to averaging the LBM-processed TE-dependent phase. This result was especially pertinent in high-susceptibility venous regions.ConclusionFor multi-echo QSM, we recommend combining the signal phase by nonlinear fitting before applying LBMs.
Facultative release from developmental constraints through polyphenism promotes adaptively flexible maturation
Authors: Rhebergen Flor T. , Smallegange Isabel M. 
Published: June 2021

AbstractThe timing of maturation, a critical fitness determinant, is influenced by developmental and energetic constraints, particularly when growth is poor in adverse conditions. Such constraints can be altered through developmental plasticity. Thus, in theory, plasticity in energetically costly sexually selected morphologies can promote life history flexibility in variable environments. We experimentally tested this hypothesis in bulb mites(Rhizoglyphus robini)that polyphenically develop as armed fighters with enlarged legs or as scramblers without modified legs. We found that (i) mites enter metamorphosis earlier if they develop as scramblers, (ii) mites accelerate the onset of metamorphosis when they sense resource limitation, and (iii) scrambler expression increases under increased competition for food, enabling males to mature early and escape juvenile mortality. We propose that life history plasticity can evolve through polyphenic release from sexually selected constraints, making the evolutionary dynamics of secondary sexual traits and life history traits, typically studied separately, interdependent.
Modeling Progression of Single Cell Populations Through the Cell Cycle as a Sequence of Switches
Authors: Zinovyev Andrei , Sadovsky Michail , Calzone Laurence , Fouché Aziz , Groeneveld Clarice S. , Chervov Alexander , Barillot Emmanuel , Gorban Alexander N. 
Published: June 2021

AbstractCell cycle is the most fundamental biological process underlying the existence and propagation of life in time and space. It has been an object for mathematical modeling for long, with several alternative mechanistic modeling principles suggested, describing in more or less details the known molecular mechanisms. Recently, cell cycle has been investigated at single cell level in snapshots of unsynchronized cell populations, exploiting the new methods for transcriptomic and proteomic molecular profiling. This raises a need for simplified semi-phenomenological cell cycle models, in order to formalize the processes underlying the cell cycle, at a higher abstracted level. Here we suggest a modeling framework, recapitulating the most important properties of the cell cycle as a limit trajectory of a dynamical process characterized by several internal states with switches between them. In the simplest form, this leads to a limit cycle trajectory, composed by linear segments in logarithmic coordinates describing some extensive (depending on system size) cell properties. We prove a theorem connecting the effective embedding dimensionality of the cell cycle trajectory with the number of its linear segments. We also develop a simplified kinetic model with piecewise-constant kinetic rates describing the dynamics of lumps of genes involved in S-phase and G2/M phases. We show how the developed cell cycle models can be applied to analyze the available single cell datasets and simulate certain properties of the observed cell cycle trajectories. Based on our modeling, we can predict with good accuracy the cell line doubling time from the length of cell cycle trajectory.