bluuebunny/crossref_metadata_2025 huggingface dataset:
Depth Profile Analysis of Thin Oxide Layers on Polycrystalline Fe–Cr
Authors: Zijlstra Gerrit , Šamořil Tomáš , Tesařová Hana , Ocelík Václav , De Hosson Jeff Th. M.
Published: January 2020

Surfaces of polycrystalline ferritic Fe–Cr steel with grain sizes of about 13 µm in diameter were investigated with surface sensitive techniques. Thin oxide layers, with a maximum thickness of about 100 nm, were grown by oxidation in air at temperatures up to 450°C and were subsequently characterized using time-of-flight secondary ion mass spectrometry (TOF-SIMS) and atomic force microscopy. Correlative microscopy was applied, which allows for element-specific depth profiles on selected grains with a particular crystal orientation. A strong correlation between the grain orientation and the thickness of the oxide layer was found. The sequence in the oxidation growth rate of ferritic Fe–Cr steel crystal planes is found to be {011} > {111} > {001}, which is unexpectedly opposed to known Fe-based systems. Moreover, for the first time, the Cr/Fe ratio throughout the oxide layer has been determined per grain orientation. A clear order from high to low of {001} > {111} > {011} was detected.
Development and characterization of tetraploid castor plants
Authors: Baghyalakshmi K. , Shaik Mobeen , Mohanrao Manmode Darpan , Shaw Ranjan Kumar , Lavanya C. , Manjunatha T. , Senthilvel S.
Published: January 2020

Castor is a prime industrial crop belonging to a monotypic genus and its genetic improvement depends on creating desired variability in the primary gene pool. This study reports the development of tetraploid castor plants through colchicine treatment. Seeds of three castor genotypes were soaked in aqueous solutions of colchicine with variable concentrations, and the LD50value was determined. Of 1010 treated field-raised plants, three were identified as potential polyploids based on increases in a guard cell size and reductions in the number of stomata. The putative polyploid plants were selfed and the progeny were subjected to meiotic analysis. All the progeny were found to be tetraploid. The pairing of chromosomes was abnormal with univalent to octavalent configurations during meiosis-I, but the later parts of meiosis were normal. Seasonal variations in pollen fertility indicated the possible role of temperature-sensitive male sterility in causing the sterility in tetraploid plants. The tetraploid plants were phenotypically comparable with their diploid counterparts, but produced substantially bigger seeds. Thus, these tetraploid plants are valuable resources for basic and applied research in castor.
Drill and broadcast establishment methods influence interseeded cover crop performance in organic corn
Authors: Wallace John M. , Isbell Sarah , Hoover Ron , Barbercheck Mary , Kaye Jason , Curran William S.
Published: January 2020

Organic grain producers are interested in interseeding cover crops into corn (Zea mays L.) in regions that have a narrow growing season window for post-harvest establishment of cover crops. A field experiment was replicated across 2 years on three commercial organic farms in Pennsylvania to compare the effects of drill- and broadcast-interseeding to standard grower practices, which included post-harvest seeding cereal rye (Secale cereale L.) at the more southern location and winter fallow at the more northern locations. Drill- and broadcast-interseeding treatments occurred just after last cultivation and used a cover crop mixture of annual ryegrass [Lolium perenne L. ssp. multiflorum (Lam.) Husnot] + orchardgrass (Dactylis glomerata L.) + forage radish (Raphanus sativus L. ssp. longipinnatus). Higher mean fall cover crop biomass and forage radish abundance (% of total) was observed in drill-interseeding treatments compared with broadcast-interseeding. However, corn grain yield and weed suppression and N retention in late-fall and spring were similar among interseeding treatments, which suggests that broadcast-interseeding at last cultivation has the potential to produce similar production and conservation benefits at lower labor and equipment costs in organic systems. Post-harvest seeding cereal rye resulted in greater spring biomass production and N retention compared with interseeded cover crops at the southern location, whereas variable interseeding establishment success and dominance of winter-killed forage radish produced conditions that increased the likelihood of N loss at more northern locations. Additional research is needed to contrast conservation benefits and management tradeoffs between interseeding and post-harvest establishment methods.
Multiple uses of app instead of using multiple apps – a case for rethinking the digital health technology toolbox
Authors: Torous John , Vaidyam Aditya
Published: January 2020

There are tens of thousands of mental health-related apps available today – representing extreme duplication in this digital age. Instead of a plethora of apps, there is a need for a few that meet the needs of many. Focusing on transparency and free sharing of software, we argue that a collaborative approach towards apps can advance care through creating customisable and future proofed digital tools that allow all stakeholders to engage in their design and use.
Interval between sequential glufosinate applications influences weed control in cotton
Authors: Randell Taylor M. , Hand Lavesta C. , Vance Jenna C. , Culpepper A. Stanley
Published: January 2020

Dicamba and 2,4-D systems control many problematic weeds; however, drift to susceptible crops can be a concern in diverse production areas. Glufosinate-based systems are an alternative, but current recommended rates of glufosinate can result in variable control. Research was conducted in 2017 and 2018 to investigate the optimum time interval between sequential glufosinate applications and determine if the addition of glyphosate with glufosinate is beneficial for controlling Palmer amaranth and annual grasses in cotton. The interval between sequential applications (1, 3, 5, 7, 10, or 14 d or no second spray) was the whole plot and herbicide option (glufosinate or glufosinate plus glyphosate) was the subplot. Combined over herbicides, Palmer amaranth 15- to 20-cm tall (at four locations) was controlled 98% to 99% with sequential intervals of 1 to 7 d compared with 70% to 88% with intervals of 10 or 14 d. Lowest biomass weight and population densities were noted with 1- to 7-d intervals. Large crabgrass 15- to 20-cm tall (at five locations) was controlled 93% to 98% with glufosinate applications 3- to 7-d apart as compared with 76% to 81% with applications 10- to 14-d apart. Lowest biomass weights were observed with 1- to 7-d intervals. When glufosinate controlled grass less than 93%, adding glyphosate was beneficial. Neither interval between sequential applications nor herbicide option influenced cotton yield. Shorter time intervals between sequential application and including glyphosate can improve the effectiveness of a glufosinate-based system in managing Palmer amaranth and large crabgrass.
Off-target movement assessment of dicamba in North America
Authors: Soltani Nader , Oliveira Maxwel C. , Alves Guilherme S. , Werle Rodrigo , Norsworthy Jason K. , Sprague Christy L. , Young Bryan G. , Reynolds Daniel B. , Brown Ashli , Sikkema Peter H.
Published: January 2020

Six experiments were conducted in 2018 on field sites located in Arkansas, Indiana, Michigan, Nebraska, Ontario, and Wisconsin to evaluate the off-target movement (OTM) of dicamba under field-scale conditions. The highest estimated percentages of dicamba injury in non–dicamba-resistant (DR) soybean were 55%, 44%, 39%, 67%, 15%, and 44% injury for noncovered areas and 55%, 5%, 13%, 42%, 0%, and 41% injury for covered areas during dicamba application in Arkansas, Indiana, Michigan, Nebraska, Ontario, and Wisconsin, respectively. The level of injury generally decreased as the downwind distance increased under covered and noncovered areas at all sites. There was an estimated 10% injury in non-DR soybean at 113, 8, 11, 8, and 8 m; and estimated 1% injury at 293, 28, 71, 15, and 19 m from the edge of treated fields downwind when plants were not covered during dicamba application in Arkansas, Indiana, Michigan, Ontario, and Wisconsin, respectively. Assessment of filter-paper collectors placed from 4 to 137 m downwind from the edge of the sprayed area suggested the dicamba deposition reduced exponentially with distance. The greatest injury to non-DR soybean from dicamba OTM occurred at Nebraska and Arkansas (as far as 250 m). Non-DR soybean injury was greatest adjacent to the dicamba sprayed area, but injury decreased with no injury beyond 20 m downwind or in any other direction from the dicamba sprayed area in Indiana, Michigan, Ontario, and Wisconsin. The presence of soybean injury under covered and noncovered areas during the spray period for primary drift suggests that secondary movement of dicamba was evident at five sites. Additional research is needed to determine the exact forms of secondary movement of dicamba under different environmental conditions.
Earthquake Stress Drops From Dynamic Rupture Simulations Constrained by Observed Ground Motions
Authors: Gallovič F. , Valentová Ľ.
Published: January 2020

Stress drop characterizing dynamics of earthquake rupture propagation has various definitions and measures with a yet unclear mutual relationship. We aim to reconcile this discrepancy by analyzing synthetic dynamic rupture models generated by random sampling of the model space of spatially heterogeneous dynamic rupture parameters. An ensemble of ~1,600 dynamic models, with waveforms statistically fitting empirical Ground Motion Prediction Equations, is treated as a synthetic event database. The events exhibit various magnitudes, degrees of complexity, and realistic ω−2 spectral decay of their average moment rates. While the variability of the stress drop Δτe estimated from the moment rates agrees with real data studies (
, the true static stress drops Δτs evaluated directly from the dynamic models exhibit larger values and lower variability (
). Our study suggests that the disagreement between various stress drop definitions is related to the source model approximation and not to any particular data processing.
Melt Segregation and Depletion During Ascent of Buoyant Diapirs in Subduction Zones
Authors: Zhang Nan , Behn Mark D. , Parmentier E. Marc , Kincaid Christopher
Published: January 2020

Cold, low‐density diapirs arising from hydrated mantle and/or subducted sediments on the top of subducting slabs have been invoked to transport key chemical signatures to the source region of arc magmas. However, to date there have been few quantitative models to constrain melting in such diapirs. Here we use a two‐phase Darcy‐Stokes‐energy model to investigate thermal evolution, melting, and depletion in a buoyant sediment diapir ascending through the mantle wedge. Using a simplified 2‐D circular geometry, we investigate diapir evolution in three scenarios with increasing complexity. In the first two scenarios we consider instantaneous heating of a diapir by thermal diffusion with and without the effect of the latent heat of melting. Then, these simplified calculations are compared to numerical simulations that include melting, melt segregation, and the influence of depletion on the sediment solidus along pressure‐temperature‐time (P‐T‐t) paths appropriate for ascent through the mantle wedge. The high boundary temperature induces a rim of high porosity, into which new melts are focused and then migrate upward. The rim thus acts like an annulus melt channel, while the effect of depletion buffers additional melt production. Solid matrix flow combined with recrystallization of melt pooled near the top of the diapir can result in large gradients in depletion across the diapir. These large depletion gradients can either be preserved if the diapir leaks melt during ascent, or rehomogenized in a sealed diapir. Overall our numerical simulations predict less melt production than the simplified thermal diffusion calculations. Specifically, we show that diapirs whose ascent paths favor melting beneath the volcanic arc will undergo no more than ~40–50% total melting.
Quartz Cementation in Polycrystalline Sandstone: Insights From Phase‐Field Simulations
Authors: Prajapati Nishant , Abad Gonzalez Andres , Selzer Michael , Nestler Britta , Busch Benjamin , Hilgers Christoph
Published: January 2020

Present work investigates the dynamics of polycrystalline quartz cement growth in sandstone using a multiphase‐field model. First, the model parameters corresponding to common reservoir temperature and pressure conditions were determined. A parameter related to growth kinetics was ascertained through undisturbed cement growth simulations to aptly capture the known faceting‐dependent growth behavior of quartz. Unrestricted growth simulations for different grain sizes, number of subgrains, and their crystallographic orientations revealed that (I) the model successfully recovers the tendency of quartz cements to grow at a faster overall rate on a coarse grain as compared to finer one and (II) the impact of crystallographic orientations of individual subgrains in polycrystalline grains on cement volume increases with increasing number of subgrains. For applying the model to realistic multigrain systems, we generated digital grain packs through a systematic procedure. These packs fairly represent natural sandstone in terms of grain shapes, sizes, and depositional porosity. The simulated textures in these packs resemble natural samples in terms of crystal morphologies and pore geometries. The cement growth rate decreases with the increase in fraction of polycrystalline grains, indicating a significant role of mutual hindrance among differently oriented overgrowths originating from different subgrains. Further, the permeabilities computed using fluid‐flow simulations through the progressively cemented packs suggest that monocrystalline packs are more permeable than equally porous polycrystalline ones. The computed permeabilities of the simulated microstructures are consistent with the measured permeabilities, advocating the pack generation process and cementation modeling approach.
Feasibility of Improving Groundwater Modeling by Assimilating Evapotranspiration Rates
Authors: Gelsinari Simone , Doble Rebecca , Daly Edoardo , Pauwels Valentijn R. N.
Published: January 2020

Water table dynamics are linked to the atmosphere through evapotranspiration and recharge. The assimilation of observed evapotranspiration values should thus improve groundwater model results. This paper presents a method for assimilating evapotranspiration data into a coupled unsaturated zone and groundwater model using the ensemble Kalman filter. The method is tested for a synthetically generated losing stream system in climatic conditions common in South Australia. The study focused on areas with a deep (recharge area) and a shallow (extraction area) water table and an intermediate area showing seasonal variations between these two (transition area). The data assimilation algorithm consistently improved the model states in the three areas when the ensemble spread was adequate. Improvements were also obtained in the calculation of net recharge and modeled actual evapotranspiration. The results indicate the potential to improve groundwater models using remote sensing observations of actual evapotranspiration values.
Correction: Quantitative distribution of patient-derived leukemia clones in murine xenografts revealed by cellular barcodes
Authors: Jacobs Sabrina , Ausema Albertina , Zwart Erik , Weersing Ellen , Kingma Maaike J. , El Menshawi Yasmine A. S. , de Haan Gerald , Bystrykh Leonid V. , Belderbos Mirjam E.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A role for CBFβ in maintaining the metastatic phenotype of breast cancer cells
Authors: Ran Ran , Harrison Hannah , Syamimi Ariffin Nur , Ayub Rahna , Pegg Henry J. , Deng Wensheng , Mastro Andrea , Ottewell Penny D. , Mason Susan M. , Blyth Karen , Holen Ingunn , Shore Paul
Published: January 2020

Epithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a major role in metastasis. Here we show, using MDA-MB-231 cells as a model, that the plasticity of at least some metastatic breast cancer cells is dependent on the transcriptional co-regulator CBFβ. We demonstrate that CBFβ is essential to maintain the mesenchymal phenotype of triple-negative breast cancer cells and that CBFβ-depleted cells undergo a mesenchymal to epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells. We subsequently show, using an inducible CBFβ system, that the MET can be reversed, thus demonstrating the plasticity of CBFβ-mediated EMT. Moreover, the MET can be reversed by expression of the EMT transcription factor Slug whose expression is dependent on CBFβ. Finally, we demonstrate that loss of CBFβ inhibits the ability of metastatic breast cancer cells to invade bone cell cultures and suppresses their ability to form bone metastases in vivo. Together our findings demonstrate that CBFβ can determine the plasticity of the metastatic cancer cell phenotype, suggesting that its regulation in different micro-environments may play a key role in the establishment of metastatic tumours.
B7-H7 (HHLA2) inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling
Authors: Rieder Sadiye Amcaoglu , Wang Jingya , White Natalie , Qadri Ariful , Menard Catherine , Stephens Geoffrey , Karnell Jodi L. , Rudd Christopher E. , Kolbeck Roland
Published: January 2020

Modulation of T-cell responses has played a key role in treating cancers and autoimmune diseases. Therefore, understanding how different receptors on T cells impact functional outcomes is crucial. The influence of B7-H7 (HHLA2) and CD28H (TMIGD2) on T-cell activation remains controversial. Here we examined global transcriptomic changes in human T cells induced by B7-H7. Stimulation through TCR with OKT3 and B7-H7 resulted in modest fold changes in the expression of select genes; however, these fold changes were significantly lower than those induced by OKT3 and B7-1 stimulation. The transcriptional changes induced by OKT3 and B7-H7 were insufficient to provide functional stimulation as measured by evaluating T-cell proliferation and cytokine production. Interestingly, B7-H7 was coinhibitory when simultaneously combined with TCR and CD28 stimulation. This inhibitory activity was comparable to that observed with PD-L1. Finally, in physiological assays using T cells and APCs, blockade of B7-H7 enhanced T-cell activation and proliferation, demonstrating that this ligand acts as a break signal. Our work defines that the transcriptomic changes induced by B7-H7 are insufficient to support full costimulation with TCR signaling and, instead, B7-H7 inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling.
Triple-synergistic 2D material-based dual-delivery antibiotic platform
Authors: Han Fengqi , Lv Shupei , Li Zhanrong , Jin Lin , Fan Bingbing , Zhang Junjie , Zhang Rui , Zhang Xingcai , Han Lei , Li Jingguo
Published: January 2020

Two-dimensional (2D) nanomaterials have raised significant interest in not only energy and environmental fields but also biomedical areas. Among these materials, one type that has many interesting properties and possesses numerous exciting applications is graphene oxide (GO)-based 2D materials. However, their poor stability in aqueous solutions and weak bioactivities limit their use in biomedical applications, especially antimicrobial fields. In this study, GO was functionalized with hydrophilic polymers and used as a vector for silver nanoparticles (Ag NPs) and sulfadiazine (SD). The stability of the material in aqueous solutions was greatly improved. The antibacterial activity of the novel hybrid antibacterial system (HAS) was enhanced by over 3 times compared to that of the system lacking SD. The antibacterial performance of the HAS was due to the triple synergy: bacterial capping, puncture, and inhibition. This study provides new insights into the design and fabrication of surface-modified GO and carbon materials and their 2D hybrid multifunctional materials for advanced applications including biomedical and especially antibacterial applications, broadening the design and application scope of carbon and 2D materials.
Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist
Authors: Parisi Giulia , Saco Justin D. , Salazar Felix B. , Tsoi Jennifer , Krystofinski Paige , Puig-Saus Cristina , Zhang Ruixue , Zhou Jing , Cheung-Lau Gardenia C. , Garcia Alejandro J. , Grasso Catherine S. , Tavaré Richard , Hu-Lieskovan Siwen , Mackay Sean , Zalevsky Jonathan , Bernatchez Chantale , Diab Adi , Wu Anna M. , Comin-Anduix Begoña , Charych Deborah , Ribas Antoni
Published: January 2020

Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported by NKTR-214 increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increases the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a phase 1 trial. In conclusion, NKTR-214 may have the potential to improve the antitumor activity of ACT in humans through increased in vivo expansion and polyfunctionality of the adoptively transferred T cells.
Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models
Authors: Li Ru , Huang Yujie , Lin Jun
Published: January 2020

Metastasis can occur following surgical resection of solid tumors and metastasis is the main cause of cancer death. The role of anesthetics used during surgery in cancer metastasis and the underlying mechanism remains largely unknown. Here we show that surgical dissection of primary tumors in mice under anesthesia with sevoflurane leads to significantly more lung metastasis than with propofol in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. Sevoflurane increases the level of serum IL-6, which activates STAT3 and the infiltration of CD11b+ myeloid cells into the lung. Interruption of IL-6/JAK/STAT3 pathway by a JAK inhibitor AZD1480 reverses the pro-metastatic effect of sevoflurane and the associated increase of both activated STAT3 and infiltrated CD11b+ cells in 4T1 model. Our study provides the preclinical evidence informing the distinct effects of anesthetics on metastasis of breast cancers through change of cytokines and the tumor microenvironment.
The anterior insular cortex unilaterally controls feeding in response to aversive visceral stimuli in mice
Authors: Wu Yu , Chen Changwan , Chen Ming , Qian Kai , Lv Xinyou , Wang Haiting , Jiang Lifei , Yu Lina , Zhuo Min , Qiu Shuang
Published: January 2020

Reduced food intake is common to many pathological conditions, such as infection and toxin exposure. However, cortical circuits that mediate feeding responses to these threats are less investigated. The anterior insular cortex (aIC) is a core region that integrates interoceptive states and emotional awareness and consequently guides behavioral responses. Here, we demonstrate that the right-side aIC CamKII+ (aICCamKII) neurons in mice are activated by aversive visceral signals. Hyperactivation of the right-side aICCamKII neurons attenuates food consumption, while inhibition of these neurons increases feeding and reverses aversive stimuli-induced anorexia and weight loss. Similar manipulation at the left-side aIC does not cause significant behavioral changes. Furthermore, virus tracing reveals that aICCamKII neurons project directly to the vGluT2+ neurons in the lateral hypothalamus (LH), and the right-side aICCamKII-to-LH pathway mediates feeding suppression. Our studies uncover a circuit from the cortex to the hypothalamus that senses aversive visceral signals and controls feeding behavior.
The in vivo genetic program of murine primordial lung epithelial progenitors
Authors: Ikonomou Laertis , Herriges Michael J. , Lewandowski Sara L. , Marsland Robert , Villacorta-Martin Carlos , Caballero Ignacio S. , Frank David B. , Sanghrajka Reeti M. , Dame Keri , Kańduła Maciej M. , Hicks-Berthet Julia , Lawton Matthew L. , Christodoulou Constantina , Fabian Attila J. , Kolaczyk Eric , Varelas Xaralabos , Morrisey Edward E. , Shannon John M. , Mehta Pankaj , Kotton Darrell N.
Published: January 2020

Multipotent Nkx2-1-positive lung epithelial primordial progenitors of the foregut endoderm are thought to be the developmental precursors to all adult lung epithelial lineages. However, little is known about the global transcriptomic programs or gene networks that regulate these gateway progenitors in vivo. Here we use bulk RNA-sequencing to describe the unique genetic program of in vivo murine lung primordial progenitors and computationally identify signaling pathways, such as Wnt and Tgf-β superfamily pathways, that are involved in their cell-fate determination from pre-specified embryonic foregut. We integrate this information in computational models to generate in vitro engineered lung primordial progenitors from mouse pluripotent stem cells, improving the fidelity of the resulting cells through unbiased, easy-to-interpret similarity scores and modulation of cell culture conditions, including substratum elastic modulus and extracellular matrix composition. The methodology proposed here can have wide applicability to the in vitro derivation of bona fide tissue progenitors of all germ layers.
Shoot-to-root mobile CEPD-like 2 integrates shoot nitrogen status to systemically regulate nitrate uptake in Arabidopsis
Authors: Ota Ryosuke , Ohkubo Yuri , Yamashita Yasuko , Ogawa-Ohnishi Mari , Matsubayashi Yoshikatsu
Published: January 2020

Plants modulate the efficiency of root nitrogen (N) acquisition in response to shoot N demand. However, molecular components directly involved in this shoot-to-root communication remain to be identified. Here, we show that phloem-mobile CEPD-like 2 (CEPDL2) polypeptide is upregulated in the leaf vasculature in response to decreased shoot N status and, after translocation to the roots, promotes high-affinity uptake and root-to-shoot transport of nitrate. Loss of CEPDL2 leads to a reduction in shoot nitrate content and plant biomass. CEPDL2 contributes to N acquisition cooperatively with CEPD1 and CEPD2 which mediate root N status, and the complete loss of all three proteins severely impairs N homeostasis in plants. Reciprocal grafting analysis provides conclusive evidence that the shoot CEPDL2/CEPD1/2 genotype defines the high-affinity nitrate uptake activity in root. Our results indicate that plants integrate shoot N status and root N status in leaves and systemically regulate the efficiency of root N acquisition.
Strong and fragile topological Dirac semimetals with higher-order Fermi arcs
Authors: Wieder Benjamin J. , Wang Zhijun , Cano Jennifer , Dai Xi , Schoop Leslie M. , Bradlyn Barry , Bernevig B. Andrei
Published: January 2020

Dirac and Weyl semimetals both exhibit arc-like surface states. However, whereas the surface Fermi arcs in Weyl semimetals are topological consequences of the Weyl points themselves, the surface Fermi arcs in Dirac semimetals are not directly related to the bulk Dirac points, raising the question of whether there exists a topological bulk-boundary correspondence for Dirac semimetals. In this work, we discover that strong and fragile topological Dirac semimetals exhibit one-dimensional (1D) higher-order hinge Fermi arcs (HOFAs) as universal, direct consequences of their bulk 3D Dirac points. To predict HOFAs coexisting with topological surface states in solid-state Dirac semimetals, we introduce and layer a spinful model of an s–d-hybridized quadrupole insulator (QI). We develop a rigorous nested Jackiw–Rebbi formulation of QIs and HOFA states. Employing ab initio calculations, we demonstrate HOFAs in both the room- (α) and intermediate-temperature (α″) phases of Cd3As2, KMgBi, and rutile-structure ($$ \beta ^{\prime} $$

β

′

-) PtO2.
Early life experiences selectively mature learning and memory abilities
Authors: Bessières Benjamin , Travaglia Alessio , Mowery Todd M. , Zhang Xinying , Alberini Cristina M.
Published: January 2020

The mechanisms underlying the maturation of learning and memory abilities are poorly understood. Here we show that episodic learning produces unique biological changes in the hippocampus of infant rats and mice compared to juveniles and adults. These changes include persistent neuronal activation, BDNF-dependent increase in the excitatory synapse markers synaptophysin and PSD-95, and significant maturation of AMPA receptor synaptic responses. Inhibition of PSD-95 induction following learning impairs both AMPA receptor response maturation and infantile memory, indicating that the synapse formation/maturation is necessary for creating infantile memories. Conversely, capturing the learning-induced changes by presenting a subsequent learning experience or by chemogenetic activation of the neural ensembles tagged by learning matures memory functional competence. This memory competence is selective for the type of experience encountered, as it transfers within similar hippocampus-dependent learning domains but not to other hippocampus-dependent types of learning. Thus, experiences in early life produce selective maturation of memory abilities.
Structural insights into selective interaction between type IIa receptor protein tyrosine phosphatases and Liprin-α
Authors: Wakita Maiko , Yamagata Atsushi , Shiroshima Tomoko , Izumi Hironori , Maeda Asami , Sendo Mizuki , Imai Ayako , Kubota Keiko , Goto-Ito Sakurako , Sato Yusuke , Mori Hisashi , Yoshida Tomoyuki , Fukai Shuya
Published: January 2020

Synapse formation is induced by transsynaptic interaction of neuronal cell-adhesion molecules termed synaptic organizers. Type IIa receptor protein tyrosine phosphatases (IIa RPTPs) function as presynaptic organizers. The cytoplasmic domain of IIa RPTPs consists of two phosphatase domains, and the membrane-distal one (D2) is essential for synapse formation. Liprin-α, which is an active zone protein critical for synapse formation, interacts with D2 via its C-terminal domain composed of three tandem sterile alpha motifs (tSAM). Structural mechanisms of this critical interaction for synapse formation remain elusive. Here, we report the crystal structure of the complex between mouse PTPδ D2 and Liprin-α3 tSAM at 1.91 Å resolution. PTPδ D2 interacts with the N-terminal helix and the first and second SAMs (SAM1 and SAM2, respectively) of Liprin-α3. Structure-based mutational analyses in vitro and in cellulo demonstrate that the interactions with Liprin-α SAM1 and SAM2 are essential for the binding and synaptogenic activity.
Synthesis of ppGpp impacts type IX secretion and biofilm matrix formation in Porphyromonas gingivalis
Authors: Kim Hey-Min , Davey Mary E.
Published: January 2020

In order to persist, bacteria need to adjust their physiological state in response to external and internal cues. External stimuli are often referred to as stressors. The stringent response, mediated by the alarmone (p)ppGpp, is central to the stress response in many bacteria; yet, there is limited knowledge regarding the role of (p)ppGpp signaling in bacteria belonging to the phylum Bacteroidetes. Like its counterparts in the gut (e.g., Bacteroides thetaiotaomicron and Bacteroides fragilis), Porphyromonas gingivalis persists in close association with its human host. Given the potential for numerous perturbations in the oral cavity, and the fact that P. gingivalis can enter and replicate within host cells, we hypothesized that (p)ppGpp is a key signaling molecule for stress adaptation and persistence. Here, we show that accumulation of ppGpp in P. gingivalis is governed by two homologous enzymes, designated Rel, and RshB, and that ppGpp signaling affects growth rate, survival, biofilm formation, production of outer membrane vesicles, and expression of genes encoding type IX secretion structural and cargo proteins. Overall, our findings provide a potential mechanism by which biofilm formation and virulence of P. gingivalis are integrated via ppGpp signaling, a regulatory mechanism central to bacterial survival in dynamic environments.
Quantifying Reoxygenation in Pancreatic Cancer During Stereotactic Body Radiotherapy
Authors: Taylor Edward , Zhou Jitao , Lindsay Patricia , Foltz Warren , Cheung May , Siddiqui Iram , Hosni Ali , Amir Ahmed El , Kim John , Hill Richard P. , Jaffray David A. , Hedley David W.
Published: January 2020

Hypoxia, the state of low oxygenation that often arises in solid tumours due to their high metabolism and irregular vasculature, is a major contributor to the resistance of tumours to radiation therapy (RT) and other treatments. Conventional RT extends treatment over several weeks or more, and nominally allows time for oxygen levels to increase (“reoxygenation”) as cancer cells are killed by RT, mitigating the impact of hypoxia. Recent advances in RT have led to an increase in the use stereotactic body radiotherapy (SBRT), which delivers high doses in five or fewer fractions. For cancers such as pancreatic adenocarcinoma for which hypoxia varies significantly between patients, SBRT might not be optimal, depending on the extent to which reoxygenation occurs during its short duration. We used fluoro-5-deoxy-α-D-arabinofuranosyl)-2-nitroimidazole positron-emission tomography (FAZA-PET) imaging to quantify hypoxia before and after 5-fraction SBRT delivered to patient-derived pancreatic cancer xenografts orthotopically implanted in mice. An imaging technique using only the pre-treatment FAZA-PET scan and repeat dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans throughout treatment was able to predict the change in hypoxia. Our results support the further testing of this technique for imaging of reoxygenation in the clinic.
Multi-platform NMR Study of Pluripotent Stem Cells Unveils Complementary Metabolic Signatures towards Differentiation
Authors: Elena-Herrmann Bénédicte , Montellier Emilie , Fages Anne , Bruck-Haimson Reut , Moussaieff Arieh
Published: January 2020

Stem cells, poised to revolutionize current medicine, stand as major workhorses for monitoring changes in cell fate. Characterizing metabolic phenotypes is key to monitor in differentiating cells transcriptional and epigenetic shifts at a functional level and provides a non-genetic means to control cell specification. Expanding the arsenal of analytical tools for metabolic profiling of cell differentiation is therefore of importance. Here, we describe the metabolome of whole pluripotent stem cells (PSCs) using high‐resolution magic angle spinning (HR-MAS), a non-destructive approach for Nuclear Magnetic Resonance (NMR) analysis. The integrated 1H NMR analysis results in detection of metabolites of various groups, including energy metabolites, amino acids, choline derivatives and short chain fatty acids. It unveils new metabolites that discriminate PSCs from differentiated counterparts and directly measures substrates and co-factors of histone modifying enzymes, suggesting that NMR stands as a strategic technique for deciphering metabolic regulations of histone post-translational modifications. HR-MAS NMR analysis of whole PSCs complements the much used solution NMR of cell extracts. Altogether, our multi-platform NMR investigation provides a consolidated picture of PSC metabolic signatures and of metabolic pathways involved in differentiation.
Safety and efficacy of stereotactic radiofrequency ablation for very large (≥8 cm) primary and metastatic liver tumors
Authors: Schullian Peter , Johnston Edward W. , Putzer Daniel , Eberle Gernot , Laimer Gregor , Bale Reto
Published: January 2020

To assess the safety and clinical outcomes of multi-probe stereotactic radiofrequency ablation (SRFA) for very large (≥8 cm) primary and metastatic liver tumors with curative treatment intent. A retrospective, single center study carried out between 01.2005 and 06.2018. 34 consecutive patients had a total of 41 primary and metastatic liver tumors with a median size of 9.0 cm (8.0–18.0 cm) at initial SRFA. Patients were treated under CT guidance using a 3D navigation system. Endpoints consisted of (i) technical efficacy; primary - requiring one treatment, and secondary – requiring two treatments (ii) complication and mortality rates (iii) local and distant recurrence (LR), (iv) disease free survival (DFS), (v) overall survival (OS). 33/41 tumors were successfully ablated at initial SRFA (80.5% primary technical efficacy rate (PTE)). Four tumors required repeat ablation, resulting in a secondary technical efficacy (STE) rate of 90.2%. Local tumor recurrence (LR) developed in 4 of 41 tumors (9.8%). The 30-day perioperative mortality was 2.3% (1/ 44 ablations). The total major complication rate was 20.5% (9 of 44 ablations). Three of nine (33.3%) major complications, such as pleural effusion, pneumothoraces or perihepatic hemorrhages were relatively easy to treat. The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 87.1%, 71.8%, and 62.8% for patients with hepatocellular carcinoma (HCC) and 87.5%, 70.0% and 70.0% for patients with intrahepatic cholangiocarcinoma (ICC) respectively. Patients with metastatic disease had OS rates of 77.8% and 22.2% at 1- and 3- years. The clinical results of SRFA in this study are encouraging and warrant a prospective multicenter study. SRFA may become one of the best therapeutic choices for a growing number of patients with primary and metastatic liver cancer.
Socioeconomic prospects of a seaweed bioeconomy in Sweden
Authors: Hasselström Linus , Thomas Jean-Baptiste , Nordström Jonas , Cervin Gunnar , Nylund Göran M. , Pavia Henrik , Gröndahl Fredrik
Published: January 2020

Seaweed cultivation is a large industry worldwide, but production in Europe is small compared to production in Asian countries. In the EU, the motivations for seaweed farming may be seen from two perspectives; one being economic growth through biomass production and the other being the provisioning of ecosystem services such as mitigating eutrophication. In this paper, we assess the economic potential of large-scale cultivation of kelp, Saccharina latissima, along the Swedish west coast, including the value of externalities. The findings suggest that seaweed farming has the potential of becoming a profitable industry in Sweden. Furthermore, large-scale seaweed farming can sequester a significant share of annual anthropogenic nitrogen and phosphorus inflows to the basins of the Swedish west coast (8% of N and 60% of P). Concerning the valuation of externalities, positive values generated from sequestration of nitrogen and phosphorus are potentially counteracted by negative values from interference with recreational values. Despite the large N and P uptake, the socioeconomic value of this sequestration is only a minor share of the potential financial value from biomass production. This suggests that e.g. payment schemes for nutrient uptake based on the socioeconomic values generated is not likely to be a tipping point for the industry. Additionally, seaweed cultivation is not a cost-efficient measure in itself to remove nutrients. Policy should thus be oriented towards industry development, as the market potential of the biomass will be the driver that may unlock these bioremediation opportunities.
Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging
Authors: Geng Li , Fan Lampson M. , Liu Fangfei , Smith Colin , Li Jian -Mei
Published: January 2020

Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ42) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ42 markedly induced BV2 cell ROS production, Nox2 expression, p47phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20–22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ42 stimulation and in aging-associated microgliosis and brain inflammation.
Publisher Correction: Clinical Features of Neuroblastoma With 11q Deletion: An Increase in Relapse Probabilities In Localized And 4S Stages
Authors: Juan Ribelles Antonio , Barberá Sandra , Yáñez Yania , Gargallo Pablo , Segura Vanessa , Juan Bárbara , Noguera Rosa , Piqueras Marta , Fornés-Ferrer Victoria , Font de Mora Jaime , Cañete Adela , Castel Victoria
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Synergistic effects of repair, resilience and retention of damage determine the conditions for replicative ageing
Authors: Borgqvist Johannes , Welkenhuysen Niek , Cvijovic Marija
Published: January 2020

Accumulation of damaged proteins is a hallmark of ageing, occurring in organisms ranging from bacteria and yeast to mammalian cells. During cell division in Saccharomyces cerevisiae, damaged proteins are retained within the mother cell, resulting in an ageing mother while a new daughter cell exhibits full replicative potential. The cell-specific features determining the ageing remain elusive. It has been suggested that the replicative ageing is dependent on the ability of the cell to repair and retain pre-existing damage. To deepen the understanding of how these factors influence the life of individual cells, we developed and experimentally validated a dynamic model of damage accumulation accounting for replicative ageing on the single cell level. The model includes five essential properties: cell growth, damage formation, damage repair, cell division and cell death, represented in a theoretical framework describing the conditions allowing for replicative ageing, starvation, immortality or clonal senescence. We introduce the resilience to damage, which can be interpreted as the difference in volume between an old and a young cell. We show that the capacity to retain damage deteriorates with high age, that asymmetric division allows for retention of damage, and that there is a trade-off between retention and the resilience property. Finally, we derive the maximal degree of asymmetry as a function of resilience, proposing that asymmetric cell division is beneficial with respect to replicative ageing as it increases the lifespan of a given organism. The proposed model contributes to a deeper understanding of the ageing process in eukaryotic organisms.
The Quantitative-Phase Dynamics of Apoptosis and Lytic Cell Death
Authors: Vicar Tomas , Raudenska Martina , Gumulec Jaromir , Balvan Jan
Published: January 2020

Cell viability and cytotoxicity assays are highly important for drug screening and cytotoxicity tests of antineoplastic or other therapeutic drugs. Even though biochemical-based tests are very helpful to obtain preliminary preview, their results should be confirmed by methods based on direct cell death assessment. In this study, time-dependent changes in quantitative phase-based parameters during cell death were determined and methodology useable for rapid and label-free assessment of direct cell death was introduced. The goal of our study was distinction between apoptosis and primary lytic cell death based on morphologic features. We have distinguished the lytic and non-lytic type of cell death according to their end-point features (Dance of Death typical for apoptosis versus swelling and membrane rupture typical for all kinds of necrosis common for necroptosis, pyroptosis, ferroptosis and accidental cell death). Our method utilizes Quantitative Phase Imaging (QPI) which enables the time-lapse observation of subtle changes in cell mass distribution. According to our results, morphological and dynamical features extracted from QPI micrographs are suitable for cell death detection (76% accuracy in comparison with manual annotation). Furthermore, based on QPI data alone and machine learning, we were able to classify typical dynamical changes of cell morphology during both caspase 3,7-dependent and -independent cell death subroutines. The main parameters used for label-free detection of these cell death modalities were cell density (pg/pixel) and average intensity change of cell pixels further designated as Cell Dynamic Score (CDS). To the best of our knowledge, this is the first study introducing CDS and cell density as a parameter typical for individual cell death subroutines with prediction accuracy 75.4% for caspase 3,7-dependent and -independent cell death.
“Diabetic striatopathy”: clinical presentations, controversy, pathogenesis, treatments, and outcomes
Authors: Chua Choon-Bing , Sun Cheuk-Kwan , Hsu Chih-Wei , Tai Yi-Cheng , Liang Chih-Yu , Tsai I-Ting
Published: January 2020

Diabetic striatopathy (DS) is a rare medical condition with ambiguous nomenclature. We searched PubMed database from 1992 to 2018 for articles describing hyperglycemia associated with chorea/ballism and/or neuroimages of striatal abnormalities. Descriptive analysis was performed on demographic/clinical characteristics, locations of striatal abnormalities on neuroimages, pathology findings, treatment strategies, and outcomes. In total, 176 patients (male:female = 1:1.7) were identified from 72 articles with mean age 67.6 ± 15.9 (range, 8–92). Among them, 96.6% had type 2 DM with 17% being newly diagnosed. Average blood glucose and glycated hemoglobin concentrations were 414 mg/dL and 13.1%, respectively. Most patients (88.1%) presented with hemichorea/hemiballism. Isolated putamen and combined putamen-caudate nucleus involvements were most common on neuroimaging studies with discrepancies between CT and MRI findings in about one-sixth of patients. Unilateral arm-leg combination was the most frequent with bilateral chorea in 9.7% of patients. Chorea and imaging anomalies did not appear concomitantly in one-tenth of patients. Successful treatment rates of chorea with glucose-control-only and additional anti-chorea medications were 25.7% and 76.2%, respectively, with an overall recurrence rate being 18.2%. The most commonly used anti-chorea drug was haloperidol. To date, four out of six pathological studies revealed evidence of hemorrhage as a probable pathogenesis.