bluuebunny/crossref_metadata_2025 huggingface dataset:
Pectobacterium atrosepticum (van Hall) Gardan et al. as a Causal Agent of Potato Blackleg in Greenland
Authors: de Neergaard Eigil , Harding Susanne , Czajkowski Robert
Published: April 2020

As a part of a blackleg and soft rot survey on potato plants cultivated in the agricultural region of Southern Greenland during the growing season of 2019 diseased potato plants and tubers were collected at six localities. Samples of plants and tubers with typical blackleg and soft rot symptoms were cut into parts weighing ca. 10–15 g each and incubated in potato enrichment broth (PEB) under anaerobic conditions for 4–7 days at ca. 20–22 °C (conditions during shipment of the samples from Greenland to Poland). After enrichment plant extracts were plated on crystal violet pectate (CVP) medium to isolate individual cavity-forming bacterial colonies. The inoculated plates were incubated at 22, 25 and 28 °C to maximize the chance of finding pectinolytic bacteria with different growth temperature optima. Cavity-forming isolates were collected and purified to pure cultures on tryptone soya agar (TSA). Ten cavity-forming isolates, named Green1 – Green10, representing isolates from symptomatic plants from different locations, were selected for analyses. The isolates gave a 434 bp. product in Pectobacterium spp.-specific PCR and a 439 bp. product in P. atrosepticum (Pba) -specific PCR. These isolates were Gram (−) rods, facultative anaerobic, catalase positive, oxidase and indole negative, grew in TSB + 5% NaCl, produced acid from lactose, maltose and raffinose. BlastN analyses of the ca. 1300 bp. 16S rDNA sequences of all 10 strains indicated a 99–100% similarity to the 16S rDNA of Pectobacterium atrosepticum. All 10 isolates caused soft rot of potato tuber slices after 72 h at 28 °C. Phylogenetic analysis based on the recA gene sequence grouped the isolates together with P. atrosepticum strains CFBP1526T and SCRI1043. This is the first report on isolation of P. atrosepticum from blackleg-diseased potato plants in Greenland. The presence of P. atrosepticum and its possible impact on potato cultivation in Greenland is discussed.
SDR-Based Readout Electronics for the ECHo Experiment
Authors: Karcher N. , Richter D. , Ahrens F. , Gartmann R. , Wegner M. , Krömer O. , Kempf S. , Enss C. , Weber M. , Sander O.
Published: April 2020

Due to their excellent energy resolution, the intrinsically fast signal rise time, the huge energy dynamic range, and the almost ideally linear detector response, metallic magnetic calorimeters (MMC)s are very well suited for a variety of applications in physics. In particular, the ECHo experiment aims to utilize large-scale MMC-based detector arrays to investigate the mass of the electron neutrino. Reading out such arrays is a challenging task which can be tackled using microwave SQUID multiplexing. Here, the detector signals are transduced into frequency shifts of superconducting microwave resonators, which can be deduced using a high-end software-defined radio (SDR) system. The ECHo SDR system is a custom-made modular electronics, which provides 400 channels equally distributed in a 4 to 8 GHz frequency band. The system consists of a superheterodyne RF frequency converter with two successive mixers, a modular conversion, and an FPGA board. For channelization, a novel heterogeneous approach, utilizing the integrated digital down conversion (DDC) of the ADC, a polyphase channelizer, and another DDC for demodulation, is proposed. This approach has excellent channelization properties while being resource-efficient at the same time. After signal demodulation, on-FPGA flux-ramp demodulation processes the signals before streaming it to the data processing and storage backend.
Genotoxicity and Safety Pharmacology Studies of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br.
Authors: Zhao Yun-Li , Su Min , Shang Jian-Hua , Wang Xia , Bao Guang-Lei , Ma Jia , Sun Qing-Di , Yuan Fang , Wang Jing-Kun , Luo Xiao-Dong
Published: April 2020

Indole alkaloids extract (IAAS) was prepared from leaves of Alstonia scholaris (L.) R. Br., an evergreen tropical plant widely distributed throughout the world. This plant has been used historically by the Dai ethnic people of China to treat respiratory diseases. This study evaluated the genotoxicity and safety pharmacology of IAAS to support clinical use. The bacterial reverse mutation (Ames) test, in vitro mammalian chromosomal aberration test, and in vivo mammalian erythrocyte micronucleus (MN) test were performed to evaluate genotoxicity. Mice were administered IAAS (240, 480, or 960 mg/kg bw) once orally to observe adverse central nervous system effects. Furthermore, beagle dogs were administered IAAS (10, 30, 60 mg/kg bw) once via the duodenum to evaluate its effects on the cardiovascular and respiratory systems. IAAS with or without S9-induced metabolic activation showed no genotoxicity in the Ames test up to 500 μg/plate, in the mammalian chromosomal aberration test up to 710 μg/mL, or in the MN test up to 800 mg/kg bw. No abnormal neurobehavioral effects were observed in mice following treatment with up to 960 mg/kg bw of IAAS. Moreover, blood pressure, heart rate, electrocardiogram parameters, and depth and rate of breathing in anesthetized beagle dogs did not differ among the IAAS doses or from the vehicle group. These data indicated that IAAS did not induce mutagenicity, clastogenicity, or genotoxicity, and no pharmaco-toxicological effects were observed in the respiratory, cardiovascular, or central nervous systems. Our results increased understanding of safety considerations associated with IAAS, and may indicate that IAAS is a possible drug candidate.

Graphic Abstract
The whence and whither of marine spatial planning: revisiting the social reconstruction of the marine environment in the UK
Authors: Ritchie Heather , McElduff Linda
Published: April 2020

With the concept of marine spatial planning (MSP) firmly established in the UK with its own legislation, policies and plans underway, this paper critically revisits MSP as part of the wider debate associated with the social reconstruction of the marine environment, as first discussed by Peel and Lloyd’s seminal paper in 2004. We propose that their identified ‘marine problem’ remains and indeed has exacerbated. We ascertain that there has been much change in the governance of the marine environment that has both positively and negatively altered the way that society has (re)constructed solutions to that marine problem. We revisit Hannigan’s (1995) social constructionist framework, showing the degree to which the prerequisites have been satisfied, by providing an overview of how the marine problem has intensified in the preceding 15 years and how the marine problem has now captured the wider public’s attention. We then look at the how the response to the marine problem has evolved by examining at the current marine planning arrangements across the UK. We conclude by stating that the whence of MSP is clear, culminating with the formal introduction of MSP in the UK which has positively altered the way in which the marine environment is socially reconstructed. The whither is much more unclear. With a continually rapidly moving agenda of change, there is much more to be done for us to say that the marine problem has been successfully socially reconstructed.
Allen: A High-Level Trigger on GPUs for LHCb
Authors: Aaij R. , Albrecht J. , Belous M. , Billoir P. , Boettcher T. , Brea Rodríguez A. , vom Bruch D. , Cámpora Pérez D. H. , Casais Vidal A. , Craik D. C. , Fernandez Declara P. , Funke L. , Gligorov V. V. , Jashal B. , Kazeev N. , Martínez Santos D. , Pisani F. , Pliushchenko D. , Popov S. , Quagliani R. , Rangel M. , Reiss F. , Sánchez Mayordomo C. , Schwemmer R. , Sokoloff M. , Stevens H. , Ustyuzhanin A. , Vilasís Cardona X. , Williams M.
Published: April 2020

We describe a fully GPU-based implementation of the first level trigger for the upgrade of the LHCb detector, due to start data taking in 2021. We demonstrate that our implementation, named Allen, can process the 40 Tbit/s data rate of the upgraded LHCb detector and perform a wide variety of pattern recognition tasks. These include finding the trajectories of charged particles, finding proton–proton collision points, identifying particles as hadrons or muons, and finding the displaced decay vertices of long-lived particles. We further demonstrate that Allen can be implemented in around 500 scientific or consumer GPU cards, that it is not I/O bound, and can be operated at the full LHC collision rate of 30 MHz. Allen is the first complete high-throughput GPU trigger proposed for a HEP experiment.
Influence of Different Types of Small-Size Defects on Propagation of Macro-cracks in Brittle Materials
Authors: Karpenko Olena , Oterkus Selda , Oterkus Erkan
Published: April 2020

The presence of defects in the structure requires noticeable attention and understanding of fracture mechanisms in brittle materials has to be established. Defects in the form of holes, macro- and micro-cracks are the main interest of this paper. This work investigates the dual role of holes and micro-crack arrays on toughening and degradation mechanisms in concrete structures. An ordinary state-based peridynamics (PD) model is utilized to analyse the fracture problem at the micro-level. The application of PD shows its advantage in crack-hole, macro- and micro-crack interaction problems since PD can accurately predict the contribution of defects on structural behaviour. The study of the three-point bending problem with five types of holes existing in the structure showed the crack arrest phenomena at the hole boundary and the “attraction” of the crack to propagate towards the hole. For the study of the macro- and micro-cracks interaction problem, various cases of the micro-crack distribution and inclination angles are considered and validated with analytical studies. The PD quasi-static simulations show good agreement with analytical solutions. Moreover, PD dynamic solutions show the capability of PD to capture complex crack propagation paths. It is observed that the presence of micro-cracks and holes ahead of the main crack can suppress its further propagation as well as have an influence on the crack propagation direction. The numerical results demonstrate the efficiency of the PD modelling of multiple crack interaction problems.
Sheet metal forming using environmentally benign lubricant
Authors: Więckowski Wojciech , Adamus Janina , Dyner Marcin
Published: April 2020

Sheet metal forming belongs to one of the most important technologies enabling the production durable but quite lightweight metal parts. The quality of the drawn parts depends on the deformed sheet metal, applied forming technology and process parameters, such as contact pressure, relative velocity, temperature or lubrication. The forming of steel (1.4021) parts using benign lubricant is analysed. The paper proposes replacing conventional mineral/synthetic lubricants with ones based on vegetable oils and boric acid. The effectiveness of the lubricants was assessed in laboratory strip drawing and cupping tests, and in production. An oil-based lubricant with an additive of boric acid is very effective in reducing frictional resistance and protecting the forming tools against galling.

Graphic abstract
IDENTIFYING THE PROFITS FOR WHICH A FIDUCIARY MUST ACCOUNT
Authors: Conaglen Matthew
Published: April 2020

This article addresses the manner in which accounts of profits are quantified when they are ordered against fiduciaries. Unlike previous scholarship, which has often sought to explain recent case law by reference to preconceived conceptual models, the present article addresses the topic by drawing on the reasoning adopted in the cases over a longer period, with a view to helping with the practical resolution of future cases, while also offering arguments drawn from that analysis as to the correct approach to the conceptual questions that arise.
The sense of moral obligation facilitates information agency and culture
Authors: Maranges Heather M. , Baumeister Roy F. , Vohs Kathleen D.
Published: April 2020

Tomasello argues that humans’ sense of moral obligation emerges early in development, relies on a shared “we,” and serves as the foundation of cooperation. This perspective complements our theoretical view of the human self as information agent. The shared “we” promotes not only proximal cooperative goals but also distal ones via the construction of shared understanding – it promotes culture.
The sense of obligation in children's testimonial learning
Authors: Li Pearl Han , Pesch Annelise , Koenig Melissa A.
Published: April 2020

We extend Tomasello's discussion of children's developing sense of obligation to testimonial learning. First, we review a battery of behaviors in testimonial exchanges that parallel those described by Tomasello. Second, we explore the variable ways in which children hold others accountable, suggestive that children's evaluations of moral and epistemic responsibilities in joint collaborative activities are distinct.
Intuitive theories inform children's beliefs about intergroup obligation
Authors: Chalik Lisa
Published: April 2020

In addition to emerging from children's direct experiences with collaborative partners and groups, children's beliefs about obligation also arise from a process of intuitive theory-building in early childhood. On this account, it is possible for at least some of children's beliefs to emerge in the absence of specific experiences where obligations are held among fellow members of a group “we.”
Does the concept of obligation develop from the inside-out or outside-in?
Authors: Rhodes Marjorie
Published: April 2020

Tomasello proposes that the concept of obligation develops “from the inside-out”: emerging first in experiences of shared agency and generalizing outward to shape children's broader understanding. Here I consider that obligation may also develop “from the outside-in,” emerging as a domain-specific instantiation of a more general conceptual bias to expect categories to prescribe how their members are supposed to behave.
Contrast to background influences predation on aposematic but not cryptic artificial caterpillars in a Brazilian coastal shrubland
Authors: Oliveira Rayane S. , Diniz Pedro , Araujo-Lima Vitor , Rosário Gabriela , Duca Charles
Published: April 2020

Aposematism and crypticity are visual defensive strategies against predation; however, the relative effectiveness of these two strategies to reduce the risk of predation is not yet fully understood. We evaluated the risk of predation for caterpillars with cryptic and aposematic colouration as well as the probability of predation relative to the natural variation of contrast with the substrate. We expected that the two models would experience similar predation attempts and that the contrast with the substrate would be negatively related to the predation on aposematic mimic models and positively to the predation of cryptic models. Overall, 224 models were laid out along a transect and exposed to predation for five consecutive days during winter and autumn. Daily predation was 11.0% (winter) and 4.8% (autumn). Significant differences were not observed between predation rates on the two model types (50.6% aposematic). Most of the predated models had arthropod marks (86.4%) and only 13.6% had bird marks. The chance of predation was higher the greater the contrast between the aposematic mimic model and the substrate, although no relationship was observed for the cryptic model. Our results suggest that the two colour patterns do not differ in their defensive effectiveness and that micro-habitat selection might define the predation risk on aposematic mimic caterpillars in environments dominated by arthropod predators.
The Many Faces of Transcendental Realism: Willaschek on Kant’s Dialectic
Authors: Chignell Andrew
Published: April 2020

After providing a brief overview of Marcus Willaschek's Kant on the Sources of Metaphysics, I critically reconstruct his account of ‘transcendental realism’ and the role that it plays in the dramatic narrative of the Critique of Pure Reason. I then lay out in detail how Willaschek generates and evaluates various versions of transcendental realism and raise some concerns about each. Next, I look at precisely how Willaschek's Kant thinks we can avoid applying the ‘supreme’ dialectical principle (for every conditioned there is a totality of conditions which is unconditioned) to the domain of appearances. Finally, I call into question Willaschek's efforts to appropriate the lessons of the Transcendental Dialectic without following Kant into transcendental idealism.
State strategies to address medicaid prescription spending: negotiated pricing vs price transparency
Authors: Noh Shihyun , Janousek Christian L. , Park Ji Hyung
Published: April 2020

This research longitudinally examines the association between levels of state Medicaid prescription spending and the state strategies intended to constrain cost increases: the negotiated pricing strategy, as indicated by state rebate programs, and the price transparency strategy, as indicated by state operation of All-Payer Claims Databases. The findings demonstrate evidence that state Medicaid prescription spending is influenced by the negotiated pricing strategy, especially Managed Care Organization (MCO) rebates under the Patient Protection and Affordable Care Act, but not influenced by the price transparency strategy. State decisions for MCO rebates, such as carving prescription benefits into managed care benefits, were effective in containing levels of Medicaid prescription spending over time, while other single- and multi-state rebate programs were not. Based on these findings, state policymakers may consider utilizing the MCO rebate program to address increases in Medicaid prescription spending.
Re‐examination of the Population, Stratigraphy, and Sequence of Mercurian Basins: Implications for Mercury's Early Impact History and Comparison With the Moon
Authors: Orgel Csilla , Fassett Caleb I. , Michael Gregory , Riedel Christian , van der Bogert Carolyn H. , Hiesinger Harald
Published: April 2020

Mercury has one of the best‐preserved impact records in the inner solar system due to the absence of an atmosphere and relatively unmodified ancient surface. However, our knowledge of the early impact record and the nature of the impacting projectiles are far from complete. To get a better understanding of the early impact history, we examined large impact basins (D ≥ 300 km) on Mercury. Here we cataloged 94 basins, 80 of which we classify as certain or probable, 1.7 times more than previously recognized. We re‐evaluate the crater densities of basins using the buffered nonsparseness correction technique, which we successfully applied for the Moon. In contrast with a previous study, we find that basins have a slightly higher N(300) crater density on Mercury than on the Moon, but similar N(500) basin densities. Based on these results and comparison with the Moon, we infer that no more than half of the basin record remains observable and basins older than Borealis have generally been erased from the basin record. Furthermore, we establish the stratigraphic relationships of basins based on N(25) crater frequencies, absolute model ages, and observations of crosscutting relationships. Similarly to our previous study on the Moon, we found no evidence for a change in the size‐frequency distribution of the impacting population; thus, our results are consistent with a single impactor population that bombarded Mercury's surface.
Early Impact Events on Chondritic Parent Bodies: Insights From NWA 11004, Reclassified as an LL7 Breccia
Authors: Li Y. , Rubin A. E. , Hsu W. , Ziegler K.
Published: April 2020

Key Points

NWA 11004, reclassified as an LL7 breccia, records a partial melting process

NWA 11004 records a late‐stage shock event at 4546 ± 34 Ma that produced undulose to weak mosaic extinction in pyroxene

The presence of type 7 chondrites in the early solar system may be ascribed to impacts on already warm parent bodies
Machine Learning‐Based Prediction of Spatiotemporal Uncertainties in Global Wind Velocity Reanalyses
Authors: Irrgang Christopher , Saynisch‐Wagner Jan , Thomas Maik
Published: April 2020

The characterization of uncertainties in geophysical quantities is an important task with widespread applications for time series prediction, numerical modeling, and data assimilation. In this context, machine learning is a powerful tool for estimating complex patterns and their evolution through time. Here, we utilize a supervised machine learning approach to dynamically predict the spatiotemporal uncertainty of near‐surface wind velocities over the ocean. A recurrent neural network (RNN) is trained with reanalyzed 10 m wind velocities and corresponding precalculated uncertainty estimates during the 2012–2016 time period. Afterward, the neural network's performance is examined by analyzing its prediction for the subsequent year 2017. Our experiments show that a recurrent neural network can capture the globally prevalent wind regimes without prior knowledge about underlying physics and learn to derive wind velocity uncertainty estimates that are only based on wind velocity trajectories. At single training locations, the RNN‐based wind uncertainties closely match with the true reference values, and the corresponding intra‐annual variations are reproduced with high accuracy. Moreover, the neural network can predict global lateral distribution of uncertainties with small mismatch values after being trained only at a few isolated locations in different dynamic regimes. The presented approach can be combined with numerical models for a cost‐efficient generation of ensemble simulations or with ensemble‐based data assimilation to sample and predict dynamically consistent error covariance information of atmospheric boundary forcings.
Assessment and Validation of Three Ionospheric Models (IRI‐2016, NeQuick2, and IGS‐GIM) From 2002 to 2018
Authors: Chen Jun , Ren Xiaodong , Zhang Xiaohong , Zhang Jincheng , Huang Liangke
Published: April 2020

It is important to confirm the accuracy and reliability of commonly used ionosphere models climatologically. In this contribution, International Global Navigation Satellite System Global Ionospheric Maps (IGSG) and two empirical models, that is, NeQuick2 and IRI‐2016, are assessed in detail by applying different assessment methods, for example, Jason2/3 ionospheric data, difference of Slant Total Electron Content (dSTEC) data derived from Global Navigation Satellite System (GNSS) phase observation, and single‐frequency precise point positioning. Compared with IGSG, the biases mainly range from −10 to 10 Total Electron Content Unit (TECU), while they are between −5 and 5 TECU on solar low‐level days for empirical models. The hourly mean biases are about −2.7 and −2.5 TECU for IRI‐2016 and NeQuick2 models, respectively. Over the oceanic region, the mean biases for IRI‐2016 and NeQuick2 models relative to Jason2/3‐Vertical Total Electron Content (VTEC) are smaller than that of IGSG. The Root Mean Square (RMS) values are 4.8 and 6.0 TECU for IGSG and empirical models relative to Jason2‐VTEC while the values are 5.4 and 6.0 TECU with relative to Jason3‐VTEC. Compared with dSTEC values derived from the selected stations, the RMS values are about 1.8 and 2.6 TECU for IGSG and empirical models, respectively. In the positioning domain, the accuracy of single‐frequency precise point positioning corrected by the three models can reach 1 m in three‐dimensional direction. The positioning accuracy is 0.17 m corrected by IGSG and 0.50 m corrected by IRI‐2016 and NeQuick2 in the horizontal direction.
Residuals to the CHAOS‐6 Geomagnetic Field Model Caused by Magnetospheric Currents During Enhanced Magnetic Activity
Authors: Lühr Hermann , Zhou Yun‐Liang
Published: April 2020

Thanks to mapping missions, like Ørsted, CHAMP, and Swarm, we have gained a detailed understanding of the geomagnetic field. High‐resolution models like POMME, GRIMM, or CHAOS are able to describe the main parts of the Earth's magnetic field reliably. These models represent well contributions from the core and crustal fields. But their validity of describing magnetospheric field effects is limited to low activity periods (Kp ~ 0–2). Here, we study the differences between CHAMP magnetic observations and the predictions from CHAOS‐6‐x9, a recent version, outside this validity range. Systematic residuals appear at times of elevated activity. Mean amplitudes at the equator grow up to 12 nT around 20 hr magnetic local time for magnetic activity around Kp = 4.7. Negative residuals are obtained in the evening to midnight sector and positive ones in the morning. A seasonal dependence of the magnetospheric currents causes more negative deflections of the residuals in the winter than in the summer hemisphere. This hemispheric asymmetry cannot be accounted for by a degree 1 spherical harmonics function. A surprising observation is that the residuals show a clear longitude dependent pattern, which changes with local time. The analysis reveals that this feature can be interpreted as a Universal Time dependence of the residuals with a peak‐to‐peak amplitude of about 8 nT and a period of 12 hr at an activity level of Kp = 4.7. All these results call for a better parameterization of the magnetospheric current effects in a geomagnetic field model that is reliable at least up to moderate activity levels.
Kirigami/origami: unfolding the new regime of advanced 3D microfabrication/nanofabrication with “folding”
Authors: Chen Shanshan , Chen Jianfeng , Zhang Xiangdong , Li Zhi-Yuan , Li Jiafang
Published: April 2020

Advanced kirigami/origami provides an automated technique for modulating the mechanical, electrical, magnetic and optical properties of existing materials, with remarkable flexibility, diversity, functionality, generality, and reconfigurability. In this paper, we review the latest progress in kirigami/origami on the microscale/nanoscale as a new platform for advanced 3D microfabrication/nanofabrication. Various stimuli of kirigami/origami, including capillary forces, residual stress, mechanical stress, responsive forces, and focussed-ion-beam irradiation-induced stress, are introduced in the microscale/nanoscale region. These stimuli enable direct 2D-to-3D transformations through folding, bending, and twisting of microstructures/nanostructures, with which the occupied spatial volume can vary by several orders of magnitude compared to the 2D precursors. As an instant and direct method, ion-beam irradiation-based tree-type and close-loop nano-kirigami is highlighted in particular. The progress in microscale/nanoscale kirigami/origami for reshaping the emerging 2D materials, as well as the potential for biological, optical and reconfigurable applications, is briefly discussed. With the unprecedented physical characteristics and applicable functionalities generated by kirigami/origami, a wide range of applications in the fields of optics, physics, biology, chemistry and engineering can be envisioned.
Autism spectrum heterogeneity: fact or artifact?
Authors: Mottron Laurent , Bzdok Danilo
Published: April 2020

The current diagnostic practices are linked to a 20-fold increase in the reported prevalence of ASD over the last 30 years. Fragmenting the autism phenotype into dimensional “autistic traits” results in the alleged recognition of autism-like symptoms in any psychiatric or neurodevelopemental condition and in individuals decreasingly distant from the typical population, and prematurely dismisses the relevance of a diagnostic threshold. Non-specific socio-communicative and repetitive DSM 5 criteria, combined with four quantitative specifiers as well as all their possible combinations, render limitless variety of presentations consistent with the categorical diagnosis of ASD. We propose several remedies to this problem: maintain a line of research on prototypical autism; limit the heterogeneity compatible with a categorical diagnosis to situations with a phenotypic overlap and a validated etiological link with prototypical autism; reintroduce the qualitative properties of autism presentations and of current dimensional specifiers, language, intelligence, comorbidity, and severity in the criteria used to diagnose autism in replacement of quantitative “social” and “repetitive” criteria; use these qualitative features combined with the clinical intuition of experts and machine-learning algorithms to differentiate coherent subgroups in today’s autism spectrum; study these subgroups separately, and then compare them; and question the autistic nature of “autistic traits”
DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer
Authors: Huang Rui-Xue , Zhou Ping-Kun
Published: April 2020

Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia–telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.
CPPU may induce gibberellin-independent parthenocarpy associated with PbRR9 in ‘Dangshansu’ pear
Authors: Cong Liu , Wu Ting , Liu Hanting , Wang Huibin , Zhang Haiqi , Zhao Guangping , Wen Yao , Shi Qianrong , Xu Lingfei , Wang Zhigang
Published: April 2020

Parthenocarpy is a valuable trait in self-incompatible plants, such as pear. N-(2-chloro-4-pyridyl)-N’-phenylurea (CPPU), a synthetic cytokinin analog, can induce parthenocarpy in pear (Pyrus spp.), but the mechanism of induction is unclear. To investigate the role of gibberellin in CPPU-induced parthenocarpy in pear, CPPU supplemented with paclobutrazol (PAC) was sprayed onto ‘Dangshansu’ pear. We found that the fruit set rate of pear treated with CPPU supplemented with PAC was identical to that in a CPPU-alone treatment group. In regard to cell development, CPPU mainly promoted hypanthium cell division and expansion, and PAC application had no influence on CPPU-induced cell development. RNA sequencing revealed that gibberellin 20 oxidase and gibberellin 3 oxidase genes were not differentially expressed following CPPU treatment. According to the analysis of fruit phytohormone content, the CPPU treatments did not induce gibberellin biosynthesis. These results suggest that CPPU-induced parthenocarpy may be gibberellin independent in ‘Dangshansu’ pear. After CPPU treatment, the indole acetic acid (IAA) content in fruit was significantly increased, and the abscisic acid (ABA) content was significantly decreased. Similarly, RNA sequencing revealed that many genes involved in the auxin and ABA pathways were significantly differentially expressed in the CPPU treatment groups; among them, indole-3-pyruvate monooxygenase (YUCCA) was significantly upregulated and 9-cis-epoxycarotenoid dioxygenase (NCED) was significantly downregulated. IAA and ABA may thus play important roles in CPPU-induced parthenocarpy. PbTwo-component response regulator9 (PbRR9), PbYUCCA4, and PbNCED6 were then selected to further elucidate the mechanism of CPPU-induced parthenocarpy. A yeast one-hybrid assay indicated that PbRR9 can combine with the PbYUCCA4 and PbNCED6 promoters. Dual luciferase assays revealed that PbRR9 can promote and repress the activities of the PbYUCCA4 and PbNCED6 promoters, respectively. After the transient expression of PbRR9 in fruits, PbYUCCA4 expression was significantly upregulated, and PbNCED6 expression was significantly downregulated. This study uncovered a CPPU-induced parthenocarpy mechanism that is different from that in tomato. CPPU may upregulate PbYUCCA4 and downregulate PbNCED6 by upregulating PbRR9, thereby increasing IAA content and decreasing ABA content to ultimately induce parthenocarpy in ‘Dangshansu’ pear. However, because only a single time point was used and because ‘botanical’ and ‘accessory’ fruits have different structures, this conclusion is still preliminary.
Transcriptome analysis and metabolic profiling reveal the key role of carotenoids in the petal coloration of Liriodendron tulipifera
Authors: Hao Zhaodong , Liu Siqin , Hu Lingfeng , Shi Jisen , Chen Jinhui
Published: April 2020

Liriodendron tulipifera, also known as tuliptree, is a popular ornamental horticultural plant with extraordinary tulip-shaped flowers characterized by an orange band near their base. The mechanisms underlying petal band-specific pigmentation during L. tulipifera flower development are unclear. Here, we combined nontargeted and targeted metabolomics and transcriptomics to identify a pathway cascade leading to carotenoid biosynthesis that is specifically activated in the petal band. The comparative analysis of carotenoid metabolites between L. tulipifera and Liriodendron hybrids indicates that γ-carotene, a rare carotene in plants, is the most likely orange pigment responsible for the coloration of the petal band. Phenotypic and transcriptomic analyses of developing petals reveal that the band area is first predefined by the loss of green color. Later, the band is maintained by locally activating and repressing carotenoid and chlorophyll biosynthesis genes, respectively. Two rate-limiting genes of carotene biosynthesis, carotenoid isomerase (CRTISO) and epsilon lycopene cyclase (ε-LCY), encode the core enzymes responsible for petal band-specific orange pigmentation in L. tulipifera. In particular, a putative additional ε-LCY copy specific to L. tulipifera may contribute to the distinct petal coloration pattern, compared with L. chinense. Taken together, our work provides a first glimpse of the metabolome and transcriptome dynamics in tuliptree flower coloration and provides a valuable resource for flower breeding or metabolic engineering as well as for understanding flower evolution in an early woody angiosperm.
Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation
Authors: Seo Jai Woong , Ingham Elizabeth S. , Mahakian Lisa , Tumbale Spencer , Wu Bo , Aghevlian Sadaf , Shams Shahin , Baikoghli Mo , Jain Poorva , Ding Xiaozhe , Goeden Nick , Dobreva Tatyana , Flytzanis Nicholas C. , Chavez Michael , Singhal Kratika , Leib Ryan , James Michelle L. , Segal David J. , Cheng R. Holland , Silva Eduardo A. , Gradinaru Viviana , Ferrara Katherine W.
Published: April 2020

Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t1/2 = 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design.
Combining high-resolution scanning tunnelling microscopy and first-principles simulations to identify halogen bonding
Authors: Lawrence James , Sosso Gabriele C. , Đorđević Luka , Pinfold Harry , Bonifazi Davide , Costantini Giovanni
Published: April 2020

Scanning tunnelling microscopy (STM) is commonly used to identify on-surface molecular self-assembled structures. However, its limited ability to reveal only the overall shape of molecules and their relative positions is not always enough to fully solve a supramolecular structure. Here, we analyse the assembly of a brominated polycyclic aromatic molecule on Au(111) and demonstrate that standard STM measurements cannot conclusively establish the nature of the intermolecular interactions. By performing high-resolution STM with a CO-functionalised tip, we clearly identify the location of rings and halogen atoms, determining that halogen bonding governs the assemblies. This is supported by density functional theory calculations that predict a stronger interaction energy for halogen rather than hydrogen bonding and by an electron density topology analysis that identifies characteristic features of halogen bonding. A similar approach should be able to solve many complex 2D supramolecular structures, and we predict its increasing use in molecular nanoscience at surfaces.
The negative regulator SMAX1 controls mycorrhizal symbiosis and strigolactone biosynthesis in rice
Authors: Choi Jeongmin , Lee Tak , Cho Jungnam , Servante Emily K. , Pucker Boas , Summers William , Bowden Sarah , Rahimi Mehran , An Kyungsook , An Gynheung , Bouwmeester Harro J. , Wallington Emma J. , Oldroyd Giles , Paszkowski Uta.
Published: April 2020

Most plants associate with beneficial arbuscular mycorrhizal (AM) fungi that facilitate soil nutrient acquisition. Prior to contact, partner recognition triggers reciprocal genetic remodelling to enable colonisation. The plant Dwarf14-Like (D14L) receptor conditions pre-symbiotic perception of AM fungi, and also detects the smoke constituent karrikin. D14L-dependent signalling mechanisms, underpinning AM symbiosis are unknown. Here, we present the identification of a negative regulator from rice, which operates downstream of the D14L receptor, corresponding to the homologue of the Arabidopsis thaliana Suppressor of MAX2-1 (AtSMAX1) that functions in karrikin signalling. We demonstrate that rice SMAX1 is a suppressor of AM symbiosis, negatively regulating fungal colonisation and transcription of crucial signalling components and conserved symbiosis genes. Similarly, rice SMAX1 negatively controls strigolactone biosynthesis, demonstrating an unexpected crosstalk between the strigolactone and karrikin signalling pathways. We conclude that removal of SMAX1, resulting from D14L signalling activation, de-represses essential symbiotic programmes and increases strigolactone hormone production.
Overcoming kidney organoid challenges for regenerative medicine
Authors: Geuens Thomas , van Blitterswijk Clemens A. , LaPointe Vanessa L. S.
Published: April 2020

Kidney organoids derived from human induced pluripotent stem cells bear the potential to be used as a regenerative medicine renal replacement therapy. Advances in developmental biology shed light on the complex cellular regulation during kidney morphogenesis in animal models resulting in insights that were incorporated in the development of groundbreaking protocols for the directed differentiation of human pluripotent stem cells to kidney endpoints. Moreover, further optimization efforts to improve three-dimensional culture techniques resulted in the creation of kidney organoids. Before they can find their way to the clinic, there are critical challenges to overcome. Here, we will discuss recent advances and remaining challenges for kidney organoids to become successful in regenerative medicine. An innovative combination of tissue engineering techniques with more refined insights in the developing human kidney will ultimately lead to more mature and functional kidney organoids suitable as renal replacement therapy for patients with chronic kidney disease.
Effect of precipitation on respiration of different reconstructed soils
Authors: Lei Na , Han Jichang
Published: April 2020

Respiration and hydrothermal characteristics of four reconstructed soils in barren gravel land at a site in Shaanxi Province were monitored before, during, and after two precipitation events. Both precipitation events significantly reduced soil temperature but there were great fluctuations in temperature after the second precipitation event. Moreover, precipitation increased the moisture content of the reconstructed soils. Before the first precipitation event, the soil volumetric water content was relatively stable, while it gradually decreased before the second precipitation event. The first precipitation event significantly stimulated the respiration rate for all reconstructed soils, while the second precipitation event generally inhibited it, especially during the precipitation event. The key factors influencing respiration for different reconstructed soils were different between the precipitation events. When soil volumetric water content showed persistent variation before precipitation, soil moisture was the most influential factor. In contrast, if water content was stable, soil temperature was more influential. Soil moisture and temperature jointly influenced soil respiration before, during, and after the precipitation event, while soil moisture was always the most influential factor after precipitation.
Anthropogenic Anoxic History of the Tuvalu Atoll Recorded as Annual Black Bands in Coral
Authors: Nakamura Nobuko , Kayanne Hajime , Takahashi Yoshio , Sunamura Michinari , Hosoi Go , Yamano Hiroya
Published: April 2020

Atoll islands are small, low-lying and highly vulnerable to sea level rise (SLR). Because these islands are fully composed of the skeletons from coral reef creatures, the healthy coral ecosystem plays a pivotal role in island resilience against SLR. The environmental deterioration of reefs caused by increases in the human population has been recently reported, but the timing and process are unknown. We investigated the annual black bands in a coral boring core from Fongafale Island, the capital of Tuvalu, which is a symbolic atoll country that is being submerged due to SLR. The iron redox state and microbial gene segments in the coral skeleton might be new environmental indicators that reveal the linkage between anthropogenic activity and coral reef ecosystems. Our findings provide the first demonstration that iron sulfide has formed concentrated black layers since 1991 under the seasonal anoxic conditions inside coral annual bands. Since the 1990s, increasing human activity and domestic waste-induced eutrophication has promoted sludge and/or turf algae proliferation with the subsequent seasonal destruction, resulting in sulfate reduction by anaerobic bacteria. With the recent climate variability, these anthropogenic effects have induced the mass mortality of branching corals, deteriorated the coral reef ecosystem and deprived the resilience of the island against SLR.
Small RNA sequencing revealed various microRNAs involved in ethylene-triggered flowering process in Aechmea fasciata
Authors: Ding Yuanhao , Wang Jiabin , Lei Ming , Li Zhiying , Jing Yonglin , Hu Haiyan , Zhu Sitao , Xu Li
Published: April 2020

Ethylene-triggered flowering is a common phenomenon in plants of the family Bromeliaceae, but its molecular mechanism remains unclear. As a classical group of small RNAs, microRNAs play an essential role in the regulation of flowering. In this study, we found that various miRNAs participate in the ethylene-triggered flowering process in Aechmea fasciata via small RNA sequencing using juvenile and adult plants treated with ethylene for 24 hours. Finally, 63 known miRNAs, 52 novel miRNAs and 1721 target genes were identified or predicted. Expression changes of specific miRNAs were validated by qRT-PCR and northern blotting. Some predicted targets, including SPL, GAMYB and ARF, were verified in RLM-RACE experiments. Gene Ontology (GO) and KEGG analysis showed that numerous developmental and RNA-related processes were enriched. Integrated analysis of the transcriptomic data with small RNA sequencing revealed that numerous miRNAs and targets involved in ethylene-triggered flowering in A. fasciata. Our study is helpful for illuminating the molecular basis of the ethylene-triggered flowering phenomenon in Bromeliaceae.
PETER-assay: Combined Impedimetric Detection of Permeability (PE) and Resistance (TER) of Barrier-Forming Cell Layers
Authors: Urban Florian , Hajek Kathrin , Naber Tobias , Anczykowski Boris , Schäfer Marcus , Wegener Joachim
Published: April 2020

Epithelial and endothelial barrier function is typically studied in vitro by growing the cells of interest on permeable supports that are sandwiched between two fluid compartments. This setup mimics the physiological situation with the cell layer as the diffusion barrier at the interface between two chemically distinct fluids. Routinely, the barrier function is quantitatively described by two key parameters: (i) the transepithelial or transendothelial electrical resistance (TER) as a measure of the permeability for small inorganic ions and (ii) the permeability coefficient (PE) as a descriptor of the permeability for molecular tracers. So far the two parameters have been determined in separate experiments. This study introduces a device that allows for simultaneous detection of PE and TER of the very same cell monolayer in one single experiment (PETER-assay). The novel approach is entirely based on AC impedance measurements in two different modes, so that TER and PE become available in real time. The new approach is demonstrated for three epithelial cell lines derived from the kidney (MDCK-I, MDCK-II, NRK) with very different barrier properties under stationary conditions and when challenged by barrier-breaking fungal toxin cytochalasin D. PETER provides an excellent time-resolution and completely automated data collection.