bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitrononalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems
Authors: Wen Xiaopeng , Yamanaka Makoto , Terada Shiho , Kamei Ken-ichiro 
Published: December 2020

AbstractNonalcoholic fatty liver disease (NAFLD) is one of the common chronic liver conditions, whose treatment involves curing patients without liver transplantation. Understanding the mechanism of NAFLD initiation and progression would enable development of new diagnostic tools and drugs; however, until now, the underlying mechanisms of this condition remain largely unknown owing to the lack of experimental settings that can simplify the complicated NAFLD processin vitro. Microphysiological systems (MPSs) have long been used to recapture human pathophysiological conditionsin vitrofor applications in drug discovery. However, polydimethylsiloxane (PDMS) has been used in most of these MPSs as the structural material; it absorbs hydrophobic molecules, such as free fatty acids (FFAs), which are the key components that initiate NAFLD. Therefore, the current PDMS-based MPSs cannot be directly applied toin vitroNALFD modeling. In this work, we present anin vitroNAFLD model with an MPS made of cyclo-olefin polymer (COP), namely COP-MPS, to prevent absorption of FFAs. We demonstrated induction of the NAFLD-like phenotype in HepaRG hepatocyte-like cells cultured in the COP-MPS by introducing FFAs. The FFAs induced lipid accumulation in the HepaRG cells, resulting in inactivation of the apoptotic cells. We believe that the proposed COP-MPS can contribute toward investigations of NAFLD mechanisms and identification of new drugs to prevent the progression of liver disease and avoid liver transplantation.
Assessing Pain in a Noninvasive Manner by Measuring Changes in the Microcirculation
Authors: Shainshein Dana , Shenkman Louis , Khashan Ahmed , Bennun Meir , Fine Ilya 
Published: December 2020

ABSTRACTThe quantitative determination of the level of pain is one of the most challenging clinical problems. This article proposes a method for quantitative assessment of both acute and chronic levels of pain, based on the analysis of hemodynamic patterns measured using a non-invasive sensor. Hemodynamic characteristics were taken from the finger using a sensor measuring the dynamic scattering of light from the skin surface. Changes in hemodynamic parameters in patients with chronic pain were studied. One group of patients with chronic back pain required epidural injection for pain relief. The second group of patients had a Spinal Cord Stimulator implant which was switched off one hour before arriving at the clinic. Optical signals were collected before and after pain relief, either by epidural injection or by turning on the stimulator. Both groups reported their pain level using a standard numerical rating scale. Processing of the results showed that the changes in measured hemodynamic parameters corresponded in most cases to the changes in pain reported by patients following medical intervention. The results suggest that this new non-invasive measurement of pain can be used both for physiological studies and for monitoring various categories of patients suffering from pain.
Quantifying multivariate genotype-by-environment interactions, evolutionary potential and its context-dependence in natural populations of the water flea,Daphnia magna
Authors: Brunner Franziska S. , Reynolds Alan , Wilson Ian W. , Price Stephen , Paterson Steve , Atkinson David , Plaistow Stewart J. 
Published: December 2020

ABSTRACTGenotype-by-environment interactions (G x E) underpin the evolution of plastic responses in natural populations. Theory assumes that G x E interactions exist but empirical evidence from natural populations is equivocal and difficult to interpret because G x E interactions are normally univariate plastic responses to a single environmental gradient. We compared multivariate plastic responses of 43Daphnia magnaclones from the same population in a factorial experiment that crossed temperature and food environments. Multivariate plastic responses explained more than 30% of the total phenotypic variation in each environment. G x E interactions were detected in most environment combinations irrespective of the methodology used. However, the nature of G x E interactions was context-dependent and led to environment-specific differences in additive genetic variation (G-matrices). Clones that deviated from the population average plastic response were not the same in each environmental context and there was no difference in whether clones varied in the nature (phenotypic integration) or magnitude of their plastic response in different environments. Plastic responses to food were aligned with additive genetic variation (gmax) at both temperatures, whereas plastic responses to temperature were not aligned with additive genetic variation (gmax) in either food environment. These results suggest that fundamental differences may exist in the potential for our population to evolve novel responses to food versus temperature changes, and challenges past interpretations of thermal adaptation based on univariate studies.
eIF2B Conformation and Assembly State Regulate the Integrated Stress Response
Authors: Schoof Michael , Boone Morgane , Wang Lan , Lawrence Rosalie , Frost Adam , Walter Peter 
Published: December 2020

AbstractThe integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in response to various stress conditions. Phosphorylated eIF2 (eIF2-P) inhibits eIF2’s nucleotide exchange factor eIF2B, a two-fold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assemblyin vitroandin vivo.In the absence of eIF2B’s α-subunit, the ISR is induced because unassembled eIF2B tetramer subcomplexes accumulate in cells. Upon addition of the small-molecule ISR inhibitor ISRIB, eIF2B tetramers assemble into active octamers. Surprisingly, ISRIB inhibits the ISR even in the context of fully assembled eIF2B decamers, revealing an allosteric communication between the physically distant eIF2, eIF2-P, and ISRIB binding sites. Cryo-EM structures suggest a rocking motion in eIF2B that couples these binding sites. eIF2-P binding converts eIF2B decamers into ‘conjoined tetramers’ with greatly diminished activity. Thus, ISRIB’s effects in disease models could arise from eIF2B decamer stabilization, allosteric modulation, or both.
Brain-scale emergence of slow-wave synchrony and highly responsive asynchronous states based on biologically realistic population models simulated in The Virtual Brain
Authors: Goldman Jennifer S. , Kusch Lionel , Yalcinkaya Bahar Hazal , Depannemaecker Damien , Nghiem Trang-Anh E. , Jirsa Viktor , Destexhe Alain 
Published: December 2020

ABSTRACTUnderstanding the many facets of the organization of brain dynamics at large scales remains largely unexplored. Here, we construct a brain-wide model based on recent progress in biologically-realistic population models obtained using mean-field techniques. We use The Virtual Brain (TVB) as a simulation platform and incorporate mean-field models of networks of Adaptive Exponential (AdEx) integrate-and-fire neurons. Such models can capture the main intrinsic firing properties of central neurons, such as adaptation, and also include the typical kinetics of postsynaptic conductances. We hypothesize that such features are important to a biologically realistic simulation of brain dynamics. The resulting “TVB-AdEx” model is shown here to generate two fundamental dynamical states, asynchronous-irregular (AI) and Up-Down states, which correspond to the asynchronous and synchronized dynamics of wakefulness and slow-wave sleep, respectively. The synchrony of slow waves appear as an emergent property at large scales, and reproduce the very different patterns of functional connectivity found in slow-waves compared to asynchronous states. Next, we simulated experiments with transcranial magnetic stimulation (TMS) during asynchronous and slow-wave states, and show that, like in experimental data, the effect of the stimulation greatly depends on the activity state. During slow waves, the response is strong but remains local, in contrast with asynchronous states, where the response is weaker but propagates across brain areas. To compare more quantitatively with wake and slow-wave sleep states, we compute the perturbational complexity index and show that it matches the value estimated from TMS experiments. We conclude that the TVB-AdEx model replicates some of the properties of synchrony and responsiveness seen in the human brain, and is a promising tool to study spontaneous and evoked large-scale dynamics in the normal, anesthetized or pathological brain.
High resolution copy number inference in cancer using short-molecule nanopore sequencing
Authors: Baslan Timour , Kovaka Sam , Sedlazeck Fritz J. , Zhang Yanming , Wappel Robert , Lowe Scott W. , Goodwin Sara , Schatz Michael C. 
Published: December 2020

ABSTRACTGenome copy number is an important source of genetic variation in health and disease. In cancer, clinically actionable Copy Number Alterations (CNAs) can be inferred from short-read sequencing data, enabling genomics-based precision oncology. Emerging Nanopore sequencing technologies offer the potential for broader clinical utility, for example in smaller hospitals, due to lower instrument cost, higher portability, and ease of use. Nonetheless, Nanopore sequencing devices are limited in terms of the number of retrievable sequencing reads/molecules compared to short-read sequencing platforms. This represents a challenge for applications that require high read counts such as CNA inference. To address this limitation, we targeted the sequencing of short-length DNA molecules loaded at optimized concentration in an effort to increase sequence read/molecule yield from a single nanopore run. We show that sequencing short DNA molecules reproducibly returns high read counts and allows high quality CNA inference. We demonstrate the clinical relevance of this approach by accurately inferring CNAs in acute myeloid leukemia samples. The data shows that, compared to traditional approaches such as chromosome analysis/cytogenetics, short molecule nanopore sequencing returns more sensitive, accurate copy number information in a cost effective and expeditious manner, including for multiplex samples. Our results provide a framework for the sequencing of relatively short DNA molecules on nanopore devices with applications in research and medicine, that include but are not limited to, CNAs.
Graph Theoretical Design of Biomimetic Aramid Nanofiber Nanocomposites as Insulation Coatings for Implantable Bioelectronics
Authors: Zhang Huanan , Vecchio Drew , Emre Ahmet , Rahmani Samantha , Cheng Chong , Zhu Jian , Misra Asish C. , Lahann Joerg , Kotov Nicholas A. 
Published: December 2020

AbstractAn insulation material combining crack and delamination resistance, flexibility, strong adhesion, and biocompatibility is vital for implantable bioelectronic devices of all types. Creating a material with the combination of all these properties is a particularly distinct challenge for implantable electrodes. Here we describe a nanocomposite material addressing these technological challenges based on aramid nanofibers (ANFs) whose unique mechanical properties are complemented by the epoxy resins with strong adhesion to various surfaces. The nanoscale structure of the ANF/epoxy nanocomposite coating replicates the nanofibrous organization of human cartilage, which is known for its exceptional toughness and longevity. The structural analogy between percolating networks of cartilage and ANF was demonstrated using Graph Theory (GT) analysis. The match of multiple GT indexes indicated the near identical organization pattern of cartilage and ANF/epoxy nanocomposite. When compared with the standard insulating material for bioelectronics,Parylene C,the ANF/epoxy nanocomposite demonstrates excellent interfacial adhesion, biocompatibility, and low inflammatory response. This study opens the possibility for the development of insulation materials suitable for different types of electronics for neural engineering and other biomedical applications. Also important, GT analysis makes possible structural characterization of complex biological and biomimetic materials.
Spectrum Degradation of Hippocampal LFP During Euthanasia
Authors: Zhou Y. , Sheremet A. , Kennedy J. P. , DiCola Nicholas M. , Maciel Carolina B. , Burke Sara N. , Maurer A.P. 
Published: December 2020

AbstractThe hippocampal local field potential (LFP) exhibits a strong correlation with behavior. During rest, the theta rhythm is not prominent, but during active behavior, there are strong rhythms in the theta, theta harmonics, and gamma ranges. With increasing running velocity, theta, theta harmonics and gamma increase in power and in cross-frequency coupling, suggesting that neural entrainment is a direct consequence of the total excitatory input. While it is common to study the parametric range between the LFP and its complementing power spectra between deep rest and epochs of high running velocity, it is also possible to explore how the spectra degrades as the energy is completely quenched from the system. Specifically, it is unknown whether the 1/f slope is preserved as synaptic activity becomes diminished, as low frequencies are generated by large pools of neurons while higher frequencies comprise the activity of more local neuronal populations. To test this hypothesis, we examined rat LFPs recorded from the hippocampus and entorhinal cortex during barbiturate overdose euthanasia. Within the hippocampus, the initial stage entailed a quasi-stationary stage when the LFP spectrum exhibited power-law feature while the frequency components over 20 Hz exhibited a power decay with a similar decay rate. This stage was followed by a rapid collapse of power spectrum towards the absolute electrothermal noise background. As the collapse of activity occurred later in hippocampus compared with medial entorhinal cortex or visual cortex, it suggests that the ability of a neural network to maintain the 1/f slope with decreasing energy is a function of general connectivity. Broadly, these data support the energy cascade theory where there is a cascade of energy from large cortical populations into smaller loops, such as those that supports the higher frequency gamma rhythm. As energy is pulled from the system, neural entrainment at gamma frequency (and higher) decline first. The larger loops, comprising a larger population, are fault-tolerant to a point capable of maintaining their activity before a final collapse.
Squid: Simplifying Quantitative Imaging Platform Development and Deployment
Authors: Li Hongquan , Krishnamurthy Deepak , Li Ethan , Vyas Pranav , Akireddy Nibha , Chai Chew , Prakash Manu 
Published: December 2020

AbstractWith rapid developments in microscopy methods, highly versatile, robust and affordable implementations are needed to enable rapid and wide adoption by the biological sciences community. Here we report Squid, a quantitative imaging platform with a full suite of hardware and software components and configurations for deploying facility-grade widefield microscopes with advanced features like flat field fluorescence excitation, patterned illumination and tracking microscopy, at a fraction of the cost of commercial solutions. The open and modular nature (both in hardware and in software) lowers the barrier for deployment, and importantly, simplifies development, making the system highly configurable and experiments that can run on the system easily programmable. Developed with the goal of helping translate the rapid advances in the field of microscopy and microscopy-enabled methods, including those powered by deep learning, we envision Squid will simplify roll-out of microscopy-based applications - including at point of care and in low resource settings, make adoption of new or otherwise advanced techniques easier, and significantly increase the available microscope-hours to labs.
Amyloid fibril-based hydrogels for high-throughput tumor spheroid modeling
Authors: Singh Namrata , Patel Komal , Navalkar Ambuja , Kadu Pradeep , Datta Debalina , Chatterjee Debdeep , Shaw Abhishek , Jadhav Sachin , Maji Samir K. 
Published: December 2020

AbstractBiomaterials mimicking extracellular matrices (ECM) for three-dimensional (3D) cultures have gained immense interest in tumor modeling andin vitroorgan development. Here, we introduce versatile, thixotropic amyloid hydrogels as a bio-mimetic ECM scaffold for 3D cell culture as well as high-throughput tumor spheroid formation using a drop cast method. The unique cross-β-sheet structure, sticky surface, and thixotropicity of amyloid hydrogels allow robust cell adhesion, survival, proliferation, and migration, which are essential for 3D tumor modeling with various cancer cell types. The spheroids formed show overexpression of the signature cancer biomarkers and confer higher drug resistance compared to two-dimensional (2D) monolayer cultures. Using breast tumor tissue from mouse xenograft, we showed that these hydrogels support the formation of tumor spheroids with a well-defined necrotic core, cancer-associated gene expression, higher drug resistance, and tumor heterogeneity reminiscent of the original tumor. Altogether, we have developed a rapid and cost-effective platform for generatingin vitrocancer models for the screening of anti-cancer therapeutics and developing personalized medicines.
IL-27R signaling serves as immunological checkpoint for NK cells to promote hepatocellular carcinoma
Authors: Aghayev Turan , Peshkova Iuliia O. , Mazitova Aleksandra M. , Titerina Elizaveta K. , Fatkhullina Aliia R. , Campbell Kerry S. , Grivennikov Sergei I. , Koltsova Ekaterina K. 
Published: December 2020

AbstractHepatocellular carcinoma (HCC) is the most common form of liver cancer with poor survival and limited therapeutic options. HCC has different etiologies, typically associated with viral or carcinogenic insults or fatty liver disease and underlying chronic inflammation presents as a major unifying mechanism for tumor promotion. On the other hand, mechanisms of how inflammatory response can regulate anti-cancer immunity in HCC remain incompletely understood.Interleukin (IL)-27 receptor signaling plays an anti-inflammatory role in a variety of infectious and chronic inflammatory diseases. Here, using genetic and pharmacological approaches we found that IL-27 receptor (IL-27R) signaling promotes HCC developmentin vivo. Genetic loss of IL-27R suppressed HCC development in both toxin/carcinogen-induced diethylnitrosamine (DEN) and non-alcoholic steatohepatitis (NASH)-driven models. Elevated expression of IL-27RA rendered poor prognosis to HCC patients. Mechanistically, the pro-tumorigenic effect was mediated by immunoregulatory role of IL-27R signaling within the tumor microenvironment, particularly the suppression of Natural killer (NK) cells. IL-27R ablation enhanced the accumulation and activation of cytotoxic NK cells during acute liver injury and in HCC tumors, while depletion of NK cells abrogated the effect of genetic IL-27R disruption.Taken together, our data suggest an unexpected role of IL-27R signaling as a novel immunological checkpoint regulating NK cell activity and promoting development of HCC of different etiologies.
Monkey V1 epidural field potentials provide significant information about stimulus location, size, shape, and color
Authors: Fischer Benjamin , Wegener Detlef 
Published: December 2020

AbstractBrain signal recordings with epidural microarrays constitute a low-invasive approach for recording distributed neuronal signals. Epidural field potentials (EFPs) may serve as a safe and highly beneficial signal source for a variety of research questions arising from both basic and applied neuroscience. A wider use of these signals, however, is constrained by a lack of data on their specific information content. Here, we make use of the high spatial resolution and the columnar organization of macaque primary visual cortex (V1) to investigate whether and to what extent EFP signals preserve information about various visual stimulus features. Two monkeys were presented with different feature combinations of location, size, shape, and color, yielding a total of 375 stimulus conditions. Visual features were chosen to access different spatial levels of functional organization. We found that, besides being highly specific for locational information, EFPs were significantly modulated by small differences in size, shape, and color, allowing for high stimulus classification rates even at the single-trial level. The results support the notion that EFPs constitute a low-invasive, highly beneficial signal source for longer-term recordings for medical and basic research by showing that they convey significant and reliable information about constituent features of activating stimuli.
Impact of nitrogen and phosphorus addition on resident soil and root mycobiomes in beech forests
Authors: Clausing S. , Likulunga L.E. , Janz D. , Feng H.Y. , Schneider D. , Daniel R. , Krüger J. , Lang F. , Polle A. 
Published: December 2020

AbstractIn forest soils, the pools of N and P available for microbes and plants are strongly dependent on soil properties. Here, we conducted a P and N fertilization experiment to disentangle the effects of nutrient availability on soil-residing, root-associated and ectomycorrhizal fungi in beech (Fagus sylvativa) forests differing in P availability. We tested the hypothesis that in P-poor forests, P fertilization leads to enhanced fungal diversity in soil and roots, resulting in enhanced P nutrition of beech and that N fertilization aggravates P shortage, shifting the fungal communities towards nitrophilic species. In response to fertilizer treatments (1x 50 kg ha−1P, 5x 30 kg ha−1N within 2 years), the labile P fractions increased in soil and roots, regardless of plant-available P in soil. Root total P decreased in response to N fertilization and root total P increased at the low P site in response to P addition. The relative abundances of ectomycorrhizal fungi, but not their species richness, increased in response to P or N addition in comparison with that of saprotrophic fungi. While some fungal orders (Trechisporales, Atheliales, Cantharellales) were moderately decreased in response to fertilizer treatments, Boletales increased in response to P and Russulaes to N addition. N or P fertilization resulted in functional trade-off, shifting away from saprotrophic towards symbiotrophic potential. Our results suggest that chronic exposure of forest ecosystems to increased nutrient inputs may overcome the resistance of the resident mycobiome structures resulting in nutritional imbalance and loss of forest ecosystem services.