bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging Spontaneous Imbibition in Full Darcy‐Scale Samples at Pore‐Scale Resolution by Fast X‐ray Tomography
Authors: Bartels W.‐B. , Rücker M. , Boone M. , Bultreys T. , Mahani H. , Berg S. , Hassanizadeh S. M. , Cnudde V. 
Published: July 2019

AbstractSpontaneous imbibition is a process occurring in a porous medium which describes wetting phase replacing nonwetting phase spontaneously due to capillary forces. This process is conventionally investigated by standardized, well‐established spontaneous imbibition tests. In these tests, for instance, a rock sample is surrounded by wetting fluid. The following cumulative production of nonwetting phase versus time is used as a qualitative measure for wettability. However, these test results are difficult to interpret, because many rocks do not show a homogeneous but a mixed wettability in which the wetting preference of a rock varies from location to location. Moreover, during the test the flow regime typically changes from countercurrent to cocurrent flow and no phase pressure or pressure drop can be recorded. To help interpretation, we complement Darcy‐scale production curves with X‐ray imaging to describe the differences in imbibition processes between water‐wet and mixed‐wet systems. We found that the formation of a spontaneous imbibition front occurs only for water‐wet systems; mixed‐wet systems show localized imbibition events only. The asymmetry of the front depends on the occurrence of preferred production sites, which influences interpretation. Fluid layers on the outside of mixed‐wet samples increase connectivity of the drained phase and the effect of buoyancy on spontaneous imbibition. The wider implication of our study is the demonstration of the capability of benchtop laboratory equipment to image a full Darcy‐scale experiment while at the same time obtaining pore‐scale information, resolving the natural length and time scale of the underlying processes.
Comparison Between Fluid Simulation With Test Particles and Hybrid Simulation for the Kelvin‐Helmholtz Instability
Authors: Ma Xuanye , Delamere Peter A. , Nykyri Katariina , Burkholder Brandon , Neupane Bishwa , Rice Rachel C. 
Published: July 2019

AbstractA quantitative investigation of plasma transport rate via the Kelvin‐Helmholtz (KH) instability can improve our understanding of solar‐wind‐magnetosphere coupling processes. Simulation studies provide a broad range of transport rates by using different measurements based on different initial conditions and under different plasma descriptions, which makes cross literature comparison difficult. In this study, the KH instability under similar initial and boundary conditions (i.e., applicable to the Earth's magnetopause environment) is simulated by Hall magnetohydrodynamics with test particles and hybrid simulations. Both simulations give similar particle mixing rates. However, plasma is mainly transported through a few big magnetic islands caused by KH‐driven reconnection in the fluid simulation, while magnetic islands in the hybrid simulation are small and patchy. Anisotropic temperature can be generated in the nonlinear stage of the KH instability, in which specific entropy and magnetic moment are not conserved. This can have an important consequence on the development of secondary processes within the KH instability as temperature asymmetry can provide free energy for wave growth. Thus, the double‐adiabatic theory is not applicable and a more sophisticated equation of state is desired to resolve mesoscale process (e.g., KH instability) for a better understanding of the multi‐scale coupling process.
LZTR1 facilitates polyubiquitination and degradation of RAS-GTPases
Authors: Abe Taiki , Umeki Ikumi , Kanno Shin-ichiro , Inoue Shin-ichi , Niihori Tetsuya , Aoki Yoko 
Published: July 2019

AbstractLeucine zipper-like transcriptional regulator 1 (LZTR1) encodes a member of the BTB-Kelch superfamily, which interacts with the Cullin3 (CUL3)-based E3 ubiquitin ligase complex. Mutations inLZTR1have been identified in glioblastoma, schwannomatosis, and Noonan syndrome. However, the functional role of LZTR1 in carcinogenesis or human development is not fully understood. Here, we demonstrate that LZTR1 facilitates the polyubiquitination and degradation of RAS via the ubiquitin-proteasome pathway, leading to the inhibition of the RAS/MAPK signaling. The polyubiquitination and degradation of RAS was also observed in cells expressing MRAS, HRAS, NRAS, and KRAS as well as oncogenic RAS mutants and inhibited the activation of ERK1/2 and cell growth. In vivo ubiquitination assays showed that MRAS-K127 and HRAS-K170 were ubiquitinated by LZTR1 and that the polyubiquitinated-chains contained mainly Ub-K48, K63, and K33-linked chains, suggesting its possible involvement in autophagy. Immunoprecipitation analyses showed the interaction of LZTR1 and RAS-GTPases with autophagy-related proteins, including LC3B and SQSTM1/p62. Co-expression of LZTR1 and RAS increased the expression of lipidated form of LC3B. However, long-term treatment with chloroquine had little effect on RAS protein levels, suggesting that the contribution of autophagy to LZTR1-mediated RAS degradation is minimal. Taken together, these results show that LZTR1 functions as a “RAS killer protein” mainly via the ubiquitin-proteasome pathway regardless of the type of RAS GTPase, controlling downstream signal transduction. Our results also suggest a possible association of LZTR1 and RAS-GTPases with the autophagy. These findings provide clues for the elucidation of the mechanisms of RAS degradation and regulation of the RAS/MAPK signaling cascade.
Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
Authors: Hollingsworth Scott A. , Kelly Brendan , Valant Celine , Michaelis Jordan Arthur , Mastromihalis Olivia , Thompson Geoff , Venkatakrishnan A. J. , Hertig Samuel , Scammells Peter J. , Sexton Patrick M. , Felder Christian C. , Christopoulos Arthur , Dror Ron O. 
Published: July 2019

AbstractAllosteric modulators are highly desirable as drugs, particularly for G-protein-coupled receptor (GPCR) targets, because allosteric drugs can achieve selectivity between closely related receptors. The mechanisms by which allosteric modulators achieve selectivity remain elusive, however, particularly given recent structures that reveal similar allosteric binding sites across receptors. Here we show that positive allosteric modulators (PAMs) of the M1 muscarinic acetylcholine receptor (mAChR) achieve exquisite selectivity by occupying a dynamic pocket absent in existing crystal structures. This cryptic pocket forms far more frequently in molecular dynamics simulations of the M1 mAChR than in those of other mAChRs. These observations reconcile mutagenesis data that previously appeared contradictory. Further mutagenesis experiments validate our prediction that preventing cryptic pocket opening decreases the affinity of M1-selective PAMs. Our findings suggest opportunities for the design of subtype-specific drugs exploiting cryptic pockets that open in certain receptors but not in other receptors with nearly identical static structures.
Two-step chromosome segregation in the stalked budding bacterium Hyphomonas neptunium
Authors: Jung Alexandra , Raßbach Anne , Pulpetta Revathi L. , van Teeseling Muriel C. F. , Heinrich Kristina , Sobetzko Patrick , Serrania Javier , Becker Anke , Thanbichler Martin 
Published: July 2019

AbstractChromosome segregation typically occurs after replication has finished in eukaryotes but during replication in bacteria. Here, we show that the alphaproteobacteriumHyphomonas neptunium, which proliferates by bud formation at the tip of a stalk-like cellular extension, segregates its chromosomes in a unique two-step process. First, the two sister origin regions are targeted to opposite poles of the mother cell, driven by the ParABSpartitioning system. Subsequently, once the bulk of chromosomal DNA has been replicated and the bud exceeds a certain threshold size, the cell initiates a second segregation step during which it transfers the stalk-proximal origin region through the stalk into the nascent bud compartment. Thus, while chromosome replication and segregation usually proceed concurrently in bacteria, the two processes are largely uncoupled inH. neptunium, reminiscent of eukaryotic mitosis. These results indicate that stalked budding bacteria have evolved specific mechanisms to adjust chromosome segregation to their unusual life cycle.
A standard for near-scarless plasmid construction using reusable DNA parts
Authors: Ma Xiaoqiang , Liang Hong , Cui Xiaoyi , Liu Yurou , Lu Hongyuan , Ning Wenbo , Poon Nga Yu , Ho Benjamin , Zhou Kang 
Published: July 2019

AbstractHere we report GT (Guanin/Thymine) standard (GTS) for plasmid construction under which DNA sequences are defined as two types of standard, reusable parts (fragment and barcode). We develop a technology that can efficiently add any two barcodes to two ends of any fragment without leaving scars in most cases. We can assemble up to seven such barcoded fragments into one plasmid by using one of the existing DNA assembly methods, including CLIVA, Gibson assembly, In-fusion cloning, and restriction enzyme-based methods. Plasmids constructed under GTS can be easily edited, and/or be further assembled into more complex plasmids by using standard DNA oligonucleotides (oligos). Based on 436 plasmids we constructed under GTS, the averaged accuracy of the workflow was 85.9%. GTS can also construct a library of plasmids from a set of fragments and barcodes combinatorically, which has been demonstrated to be useful for optimizing metabolic pathways.
Deleterious mutations in ALDH1L2 suggest a novel cause for neuro-ichthyotic syndrome
Authors: Sarret Catherine , Ashkavand Zahra , Paules Evan , Dorboz Imen , Pediaditakis Peter , Sumner Susan , Eymard-Pierre Eléonore , Francannet Christine , Krupenko Natalia I. , Boespflug-Tanguy Odile , Krupenko Sergey A. 
Published: July 2019

AbstractNeuro-ichthyotic syndromes are a group of rare genetic diseases mainly associated with perturbations in lipid metabolism, intracellular vesicle trafficking, or glycoprotein synthesis. Here, we report a patient with a neuro-ichthyotic syndrome associated with deleterious mutations in the ALDH1L2 (aldehyde dehydrogenase 1 family member L2) gene encoding for mitochondrial 10-formyltetrahydrofolate dehydrogenase. Using fibroblast culture established from the ALDH1L2-deficient patient, we demonstrated that the enzyme loss impaired mitochondrial function affecting both mitochondrial morphology and the pool of metabolites relevant to β-oxidation of fatty acids. Cells lacking the enzyme had distorted mitochondria, accumulated acylcarnitine derivatives and Krebs cycle intermediates, and had lower ATP and increased ADP/AMP indicative of a low energy index. Re-expression of functional ALDH1L2 enzyme in deficient cells restored the mitochondrial morphology and the metabolic profile of fibroblasts from healthy individuals. Our study underscores the role of ALDH1L2 in the maintenance of mitochondrial integrity and energy balance of the cell, and suggests the loss of the enzyme as the cause of neuro-cutaneous disease.
An unconventional uptake rate objective function approach enhances applicability of genome-scale models for mammalian cells
Authors: Chen Yiqun , McConnell Brian O. , Gayatri Dhara Venkata , Mukesh Naik Harnish , Li Chien-Ting , Antoniewicz Maciek R. , Betenbaugh Michael J. 
Published: July 2019

AbstractConstraint-based modeling has been applied to analyze metabolism of numerous organisms via flux balance analysis and genome-scale metabolic models, including mammalian cells such as the Chinese hamster ovary (CHO) cells—the principal cell factory platform for therapeutic protein production. Unfortunately, the application of genome-scale model methodologies using the conventional biomass objective function is challenged by the presence of overly-restrictive constraints, including essential amino acid exchange fluxes that can lead to improper predictions of growth rates and intracellular flux distributions. In this study, these constraints are found to be reliably predicted by an “essential nutrient minimization” approach. After modifying these constraints with the predicted minimal uptake values, a series of unconventional objective functions are applied to minimize each individual non-essential nutrient uptake rate, revealing useful insights about metabolic exchange rates and flows across different cell lines and culture conditions. This unconventional uptake-rate objective functions (UOFs) approach is able to distinguish metabolic differences between three distinct CHO cell lines (CHO-K1, -DG44, and -S) not directly observed using the conventional biomass growth maximization solutions. Further, a comparison of model predictions with experimental data from literature correctly correlates with the specific CHO-DG44-derived cell line used experimentally, and the corresponding dual prices provide fruitful information concerning coupling relationships between nutrients. The UOFs approach is likely to be particularly suited for mammalian cells and other complex organisms which contain multiple distinct essential nutrient inputs, and may offer enhanced applicability for characterizing cell metabolism and physiology as well as media optimization and biomanufacturing control.
Molecular simulation of efficient removal of H2S pollutant by cyclodextrine functionalized CNTs
Authors: Darvish Ganji Masoud , Kiyani Hadis 
Published: July 2019

AbstractDFT-D3 calculations were carried out to investigate interaction of H2S and CH4 between numerous functionalized CNTs (f-CNTs), including hydroxyl, carboxyl, and cyclodextrin groups as potential candidates for selective adsorption and elimination of toxic pollutants. It was found that pristine CNTs as well as nanotube surface of functionalized CNTs cannot stably adsorb the H2S molecule (adsorption energy of −0.17 eV). However, H2S adsorption was significantly enhanced with different magnitudes upon the functionalization of CNT. For f-CNTs, H2S adsorption was accompanied by releasing energies in the range between −0.34 to −0.54 eV where the upper limit of this range belongs to the cyclodextrin-functionalized CNT (CD-CNT) as the consequence of the existence of both dispersion and electrostatic interactions between the adsorbate and substrate. Findings also demonstrated a significantly weaker interaction between CH4 and CD-CNT in comparison to the H2S molecule with adsorption energy of −0.14 eV. Electronic properties of the selected substrates revealed no significant changes in the inherent electronic properties of the CNTs after functionalizing and adsorbing the gas molecules. Moreover, DFTB-MD simulation demonstrated high adsorption capacity as well as CD-CNT ability for H2S molecules against the CH4 one under ambient condition.
Responses of plant growth, physiological, gas exchange parameters of super and non-super rice to rhizosphere temperature at the tillering stage
Authors: Li Shuying , Jiang Haolin , Wang Jianjun , Wang Yandong , Pan Shenggang , Tian Hua , Duan Meiyang , Wang Shuli , Tang Xiangru , Mo Zhaowen 
Published: July 2019

AbstractTemperature is one of the critical factors affecting rice growth and yield production. This study investigated the effects of rhizosphere temperature at the tillering stage on the growth, physiological parameters and gas exchange attributes of two rice cultivars, i.e., the super rice cultivar Yuxiangyouzhan and the non-super rice cultivar Xiangyaxiangzhan, under hydroponic conditions. Three rhizosphere temperature treatments, i.e., a low-rhizosphere-temperature treatment (LT, nutrient solution at 17.5 ± 1.5 °C), an ambient-temperature treatment (AT, nutrient solution at 27.5 ± 1.5 °C), and a high-rhizosphere-temperature treatment (HT, nutrient solution at 37.5 ± 1.5 °C), were applied in this study. The results showed significant differences in most of the rice growth and physiological and gas exchange parameters as a result of cultivar and rhizosphere temperature as well as their interaction. In addition, the marked reduction in total dry weight was positively correlated with a notable reduction in plant morphological parameters, such as the fresh and dry weight of the leaves and stem sheaths, and changes in gas exchange parameters. Moreover, antioxidant reactions were active in response to high and low rhizosphere temperatures, which varied in different plant tissues. These results suggested that the super and non-super rice were sensitive to high and low rhizosphere temperatures, respectively.
Molecular Dynamics Study of the Changes in Conformation of Calmodulin with Calcium Binding and/or Target Recognition
Authors: Kawasaki Hiroshi , Soma Natsumi , Kretsinger Robert H. 
Published: July 2019

AbstractCalmodulin is a calcium binding protein with two lobes, N-lobe and C-lobe, which evolved from duplication and fusion of a single precursor lobe of a pair of EF-hand. These two lobes of calmodulin show subtle differences in calcium binding and target recognition; these are important for the functions of calmodulin. Since the structures, especially main chain conformations, of two EF-lobes in holo-form are quite similar; this is a good example to evaluate the effect of side chains for structural dynamics. We analyzed the structure of calmodulin using molecular dynamics and found differences in conformational ensembles between N- and C-lobes. We also showed the mutant structures created by homology modeling could reproduce the difference of dynamic motion between N- and C-lobes.
Epigenetics, N-myrystoyltransferase-1 and casein kinase-2-alpha modulates the increased replication of HIV-1 CRF02_AG, compared to subtype-B viruses
Authors: Bhargavan Biju , Kanmogne Georgette D. 
Published: July 2019

AbstractHIV subtypes distribution varies by geographic regions; this is likely associated with differences in viral fitness but the predictors and underlying mechanisms are unknown. Using in-vitro, in-vivo, and ex-vivo approaches, we found significantly higher transactivation and replication of HIV-1-CRF02_AG (prevalent throughout West-Central Africa), compared to subtype-B. While CRF02_AG-infected animals showed higher viremia, subtype-B-infected animals showed significantly more weight loss, lower CD4+ T-cells and lower CD4/CD8 ratios, suggesting that factors other than viremia contribute to immunosuppression and wasting syndrome in HIV/AIDS. Compared to HIV-1-subtype-B and its Tat proteins(Tat.B), HIV-1-CRF02_AG and Tat.AG significantly increased histone acetyl-transferase activity and promoter histones H3 and H4 acetylation. Silencing N-myrystoyltransferase(NMT)-1 and casein-kinase-(CK)-II-alpha prevented Tat.AG- and HIV-1-CRF02_AG-mediated viral transactivation and replication, but not Tat.B- or HIV-1-subtype-B-mediated effects. Tat.AG and HIV-1-CRF02_AG induced the expression of NMT-1 and CKII-alpha in human monocytes and macrophages, but Tat.B and HIV-1-subtype-B had no effect. These data demonstrate that NMT1, CKII-alpha, histone acetylation and histone acetyl-transferase modulate the increased replication of HIV-1-CRF02_AG. These novel findings demonstrate that HIV genotype influence viral replication and provide insights into the molecular mechanisms of differential HIV-1 replication. These studies underline the importance of considering the influence of viral genotypes in HIV/AIDS epidemiology, replication, and eradication strategies.
The heterogeneity in link weights may decrease the robustness of real-world complex weighted networks
Authors: Bellingeri M. , Bevacqua D. , Scotognella F. , Cassi D. 
Published: July 2019

AbstractHere we report a comprehensive analysis of the robustness of seven high-quality real-world complex weighted networks to errors and attacks toward nodes and links. We use measures of the network damage conceived for a binary (e.g. largest connected cluster LCC, and binary efficiency Effbin) or a weighted network structure (e.g. the efficiency Eff, and the total flow TF). We find that removing a very small fraction of nodes and links with respectively higher strength and weight triggers an abrupt collapse of the weighted functioning measures while measures that evaluate the binary-topological connectedness are almost unaffected. These findings unveil a problematic response-state where the attack toward a small fraction of nodes-links returns the real-world complex networks in a connected but inefficient state. Our findings unveil how the robustness may be overestimated when focusing on the connectedness of the components only. Last, to understand how the networks robustness is affected by link weights heterogeneity, we randomly assign link weights over the topological structure of the real-world networks and we find that highly heterogeneous networks show a faster efficiency decrease under nodes-links removal: i.e. the robustness of the real-world complex networks against nodes-links removal is negatively correlated with link weights heterogeneity.
Infant brain activity in response to yawning using functional near-infrared spectroscopy
Authors: Tsurumi Shuma , Kanazawa So , Yamaguchi Masami K. 
Published: July 2019

AbstractYawning is contagious in human adults. While infants do not show contagious yawning, it remains unclear whether infants perceive yawning in the same manner as other facial expressions of emotion. We addressed this problem using functional near-infrared spectroscopy (fNIRS) and behavioural experiments. We confirmed behaviourally that infants could discriminate between yawning and unfamiliar mouth movements. Furthermore, we found that the hemodynamic response of infants to a yawning movement was greater than that to mouth movement, similarly to the observations in adult fMRI study. These results suggest that the neural mechanisms underlying yawning movement perception have developed in advance of the development of contagious yawning.
Hepatoprotective effect of essential oils of Nepeta cataria L. on acetaminophen-induced liver dysfunction
Authors: Tan Juan , Li Jing , Ma Jilei , Qiao Feng 
Published: July 2019

Abstract
Nepeta cataria L. has long been used in folk food and medicine for several functions. Essential oils (EOs) were extracted from Nepeta cataria L. by supercritical fluid extraction. The results of animal experiments showed that EOs from Nepeta cataria L. significantly attenuated acetaminophen-induced liver damage. Further study confirmed that EOs were able to increase mRNA expression of uridine diphosphate glucuronosyltransferases (UGTs) and sulfotransferases (SULTs), as well as inhibit CYP2E1 activities, and thereby suppressed toxic intermediate formation. Nrf-2 activation might be involved in EOs-induced up-regulation of Phase II enzymes. Collectively, our data provide evidence that EOs protect the liver against acetaminophen-induced liver injury mainly by accelerating acetaminophen harmless metabolism, implying that EOs can be considered as a potential natural resource to develop hepatoprotective agent.