bluuebunny/crossref_metadata_2025 huggingface dataset:
The political motivations for the reform of urban policy during the rapid economic growth period in Japan: a closer look
Authors: Hasegawa Junichi
Published: December 2019

Urban policy in Japan gained greater significance in the late 1960s. In 1968, a new City Planning Law was enacted, and urban policy was a prominent issue in that year's House of Councillors election. Scholars have regarded the ruling conservative party's fear of a threat to its hegemony as the primary force driving this increased attention to urban policy. This article examines the political factors surrounding the reforms enacted, concluding that politicians actually underestimated the degree of public interest in urban policy and made largely empty political gestures to appease urban dwellers while responding more readily to agricultural interests.
The Persians. Investigating Civilisations
Authors: Wilson Andrew
Published: December 2019

Iran's geography gives it an important place in the world. To the west lie Turkey, Iraq and Syria. South is Arabia and the Persian Gulf. To the southeast is the Indian subcontinent. To the north are Russia and the Caucasus. To the northeast lie the developing states of Central Asia. To the east, Afghanistan and China.
The Representation of Föhn Events to the East of the Antarctic Peninsula in Simulations by the Antarctic Mesoscale Prediction System
Authors: Kirchgaessner Amélie , King John , Gadian Alan
Published: December 2019

Föhn winds are warm, strong, downslope winds on the leeside of mountains, which can last from several hours to a few days. The years 1995 and 2002 saw the dramatic breakup of huge parts of the Larsen Ice Shelf (LIS) on the east of the Antarctic Peninsula. It is widely accepted that hydrofracturing, the widening of crevasses due to the excess hydrostatic pressure exerted by meltwater which accumulates inside them, is the mechanism behind the breakup of the Larsen A and Larsen B ice shelves. On the LIS, in the lee of the mountain range that runs along the spine of the Antarctic Peninsula, Föhn winds are thought to provide the atmospheric conditions for significant warming over the ice shelf, leading to the initial firn densification, and subsequently providing the melt water for hydrofracturing. Measurements provide evidence that in some cases Föhn events reach an Automatic Weather Station on the LIS at over 100 km distance. In this paper, we examine the representation of Föhn events during 2011 as they were observed in measurements by an Automatic Weather Station and in simulations with the Weather Research and Forecasting Model as run for the Antarctic Mesoscale Prediction System (AMPS). We find that, while the model generally simulates meteorological parameters very well and shows good skill in capturing the occurrence, frequency, and duration of Föhn events, it underestimates the temperature increase and humidity decrease during the Föhn significantly and may thus underestimate the contribution of Föhn to driving surface melt on LIS.
A Global Survey of Apparent Aerosol‐Cloud Interaction Signals
Authors: Oreopoulos Lazaros , Cho Nayeong , Lee Dongmin
Published: December 2019

We update and expand analysis of the apparent responses to aerosol variations of the planet's cloud regimes seen by the Moderate Resolution Imaging Spectroradiometer (MODIS). We distinguish between morning aerosol loadings and afternoon clouds and consider local scales explicitly. Aerosol loading is represented by gridded aerosol optical depth (AOD) from either MODIS or a reanalysis data set, while cloud information comes exclusively from MODIS. The afternoon cloud affected quantities (CAQs) examined in conjunction with morning AOD include precipitation and cloud radiative effect, in addition to cloud properties. One analysis thrust focuses on calculating global means distinguished by morning cloud regime, of afternoon CAQs, for distinct percentiles of grid cell seasonal morning AOD distributions. When the dependence of these global means on AOD is examined, we find persistent increases in cloud radiative fluxes with AOD as predicted by classic aerosol‐cloud interaction paradigms, and also deviations from expected cloud responses, especially for precipitation. The other analysis thrust involves calculations at 1° scales of logarithmic CAQ sensitivities to AOD perturbations, approximated by linear regression slopes for distinct morning cloud regime groups. While the calculations are fundamentally local, we concentrate on the prevailing sensitivity signs in statistics of the slopes at global scales. Results from this second analysis approach indicate CAQ directions of change with AOD that are largely consistent with the first approach. When using a rather simple methodology where meteorological variables are treated as if they were CAQs, no conclusive results on the potential influence of meteorology on our findings are inferred.
Model‐Based Properties of the Dayside Open/Closed Boundary: Is There a UT‐Dependent Variation?
Authors: Smith David A. , Sojka Jan J.
Published: December 2019

The open‐closed boundary (OCB) defines a region of significant transformation in Earth's protective magnetic shield. Principle among these changes is the transition of magnetic field lines from having two foot points, one in each hemisphere, to one foot point at Earth, the other mapping to the solar wind. Charged particles in the solar wind are able to follow these open field lines into Earth's upper atmosphere. The OCB also defines the polar cap boundary. Being able to identify and track the OCB allows study of several components of the geomagnetic system. Among them are the electrodynamics of the geomagnetic field and the reconnection balance between the dayside and nightside of the geomagnetic field. Furthermore, the OCB can provide insights into the precipitation of energetic protons into the ionosphere. Using the Tsyganenko model of the geomagnetic field (T96), we demonstrate a diurnal fluctuation which we call the Universal Time (UT) effect of the OCB. This UT effect is independent of all other inputs. We anticipate this UT effect to have important consequences in modeling the OCB and other polar cap‐associated structures, especially polar cap absorption events that adversely affect high‐frequency radio wave propagation in polar regions.
Yes-associated protein regulates podocyte cell cycle re-entry and dedifferentiation in adriamycin-induced nephropathy
Authors: Xie Kewei , Xu Chenqi , Zhang Minfang , Wang Minzhou , Min Lulin , Qian Cheng , Wang Qin , Ni Zhaohui , Mou Shan , Dai Huili , Pang Huihua , Gu Leyi
Published: December 2019

Podocytes are terminally differentiated cells with little proliferative capacity. The high expression levels of cell cycle inhibitory proteins, including p21, p27, and p57, play an important role in maintaining the low level of proliferation of mature podocytes. In the present study, we aimed to explore the role of yes-associated protein (YAP) signalling in adriamycin-induced podocyte re-entry into the cell cycle and dedifferentiation. Proliferating cell nuclear antigen (PCNA)-, cyclin-dependent kinase 4 (CDK4)-, and Cyclin D1-positive podocytes were found in mice with adriamycin-induced nephropathy. In vitro, adriamycin administration increased the percentage of cells in S phase and the upregulation of mesenchymal-related marker proteins. CDK4 and cyclin D1 were significantly up-regulated after incubation with adriamycin. Overexpression of YAP in podocytes promoted their entry into the cell cycle; up-regulated cyclin D1, desmin, and snail2 expression and down-regulated Wilms’ tumour 1 (WT1) and nephrin production. Recombinant murine FGF-basic induced podocytes to re-enter the cell cycle, inhibited WT1 and nephrin, and increased desmin and snail2 expression. Pretreating podocytes with verteporfin, an inhibitor of YAP/ TEA domain transcription factor (TEAD), decreased the adriamycin-induced overexpression of cyclin D1 and reduced the ratio of S-phase podocytes. This result was further verified by knocking down YAP expression using RNA interference. In conclusion, adriamycin induced podocytes to re-enter the cell cycle via upregulation of CDK4 and cyclin D1 expression, which was at least partly mediated by YAP signalling. Re-entry into the cell cycle induced the over-expression of mesenchymal markers in podocytes.
Extensive protein S-nitrosylation associated with human pancreatic ductal adenocarcinoma pathogenesis
Authors: Tan Chaochao , Li Yunfeng , Huang Xiahe , Wei Meijin , Huang Ying , Tang Zhouqin , Huang He , Zhou Wen , Wang Yingchun , Hu Jiliang
Published: December 2019

NO (nitric oxide)-mediated protein S-nitrosylation has been established as one major signaling mechanism underlying cancer initiation and development, but its roles in PDAC (pancreatic ductal adenocarcinoma) pathogenesis still remain largely unexplored. In this study, we identified 585 unique S-nitrosylation sites among 434 proteins in PDAC patients and PANC-1 cell line by a site-specific proteomics. Larger number of S-nitrosylated proteins were identified in PDAC tissues and PANC-1 cells than adjacent non-cancerous tissues. These S-nitrosylated proteins are significantly enriched in a multitude of biological processes associated with tumorigenesis, including carbohydrate metabolism, cytoskeleton regulation, cell cycle, focal adhesion, adherent junctions, and cell migration. Components of the pancreatic cancer pathway were extensively S-nitrosylated, such as v-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) and Signal transducer and activator of transcription 3 (STAT3). Moreover, NOS (NO synthase) inhibitor significantly repressed STAT3 S-nitrosylation in PANC-1 cells, which caused significant increase of STAT3 phosphorylation and PANC-1 cell viability, suggesting important roles of protein S-nitrosylation in PDAC development. These results revealed extensive protein S-nitrosylation associated with PDAC pathogenesis, which provided a basis for protein modification-based cancer diagnosis and targeted therapy.
Side-by-side comparison of BH3-mimetics identifies MCL-1 as a key therapeutic target in AML
Authors: Ewald Larissa , Dittmann Jessica , Vogler Meike , Fulda Simone
Published: December 2019

Despite advances in the treatment of acute myeloid leukemia (AML), prognosis of AML patients is still dismal and better treatment options are required. B-cell Lymphoma 2 (BCL-2) homology domain 3 (BH3)-mimetics are emerging as a novel class of apoptosis-inducing agents that are currently being tested for the treatment of different hematological malignancies including AML. Particularly, the selective BCL-2 inhibitor ABT-199/Venetoclax is demonstrating clinical responses and has recently been approved in combination for the treatment of AML. Compounds targeting the related protein MCL-1 have recently entered clinical trials, highlighting the urgency to compare the different BH3-mimetics and identify the most promising antiapoptotic target in AML. We performed a side-by-side comparison of different highly selective and potent BH3-mimetics targeting BCL-2 (ABT-199), MCL-1 (S63845) or BCL-xL (A1331852) in a panel of AML cell lines and primary patient cells. Gene knockdown using siRNAs was utilized to investigate the functional relevance of BCL-2 proteins. Western blotting and immunoprecipitations were used to explore the influence of BH3-mimetics on interactions between pro- and antiapoptotic BCL-2 proteins. A1331852 induced apoptosis only in selected cases, indicating that BCL-xL is not a very promising therapeutic target in AML. However, S63845 displayed higher potency than ABT-199, with more cell lines and primary cells responding to S63845 than to ABT-199. MCL-1 dependency in AML cells was confirmed by siRNA-mediated knockdown of MCL-1, which was sufficient to induce apoptosis. S63845-induced cell death was accompanied by a displacement of the BH3-only protein BIM as well as BAK, resulting in BAK-dependent apoptosis. In contrast, ABT-199-induced cell death was mediated by BAX rather than BAK, indicating distinct non-redundant molecular functions of BCL-2 and MCL-1 in AML. Our study reveals that MCL-1 may be a more prevalent therapeutic target than BCL-2 in AML and identifies BIM and BAK as important mediators of S63845-induced apoptosis in AML.
Cell death following the loss of ADAR1 mediated A-to-I RNA editing is not effected by the intrinsic apoptosis pathway
Authors: Walkley Carl R. , Kile Benjamin T.
Published: December 2019

Modifications of RNA, collectively termed as the epitranscriptome, are widespread, evolutionarily conserved and contribute to gene regulation and protein diversity in healthy and disease states. There are >160 RNA modifications described, greatly exceeding the number of modifications to DNA. Of these, adenosine-to-inosine (A-to-I) RNA editing is one of the most common. There are tens of thousands of A-to-I editing sites in mouse, and millions in humans. Upon translation or sequencing an inosine base is decoded as guanosine, leading to A-to-G mismatches between the RNA and DNA. Inosine has different base pairing properties to adenosine and as a result editing not only alters the RNA code but can also change the RNA structure. In mammals A-to-I editing is performed by ADAR1 and ADAR2. A feature of murine loss of function ADAR1 alleles is cell death and a failure to survive embryogenesis. Adar1−/− and editing deficient (Adar1E861A/E861A) mice die between E11.75–13.5 of failed hematopoiesis. Strikingly this phenotype is rescued by the deletion of the cytosolic dsRNA sensor MDA5 or its downstream adaptor MAVS, a mechanism conserved in human and mouse. Current literature indicates that the loss of ADAR1 leads to cell death via apoptosis, yet this has not been genetically established. We report that blockade of the intrinsic (mitochondrial) apoptosis pathway, through the loss of both BAK and BAX, does not rescue or modify the cellular phenotype of the fetal liver or extend the lifespan of ADAR1 editing deficient embryos. We had anticipated that the loss of BAK and BAX would rescue, or at least significantly extend, the gestational viability of Adar1E861A/E861A embryos. However, the triple mutant Adar1E861A/E861ABak−/−Bax−/− embryos that were recovered at E13.5 were indistinguishable from the Adar1E861A/E861A embryos with BAK and BAX. The results indicate that cell death processes not requiring the intrinsic apoptosis pathway are triggered by MDA5 following the loss of ADAR1.
CD40 induces renal cell carcinoma-specific differential regulation of TRAF proteins, ASK1 activation and JNK/p38-mediated, ROS-dependent mitochondrial apoptosis
Authors: Ibraheem Khalidah , Yhmed Albashir M. A. , Qayyum Tahir , Bryan Nicolas P. , Georgopoulos Nikolaos T.
Published: December 2019

A unique feature of CD40 among the TNF receptor (TNFR) superfamily is its exquisitely contextual effects, as originally demonstrated in normal and malignant B-lymphocytes. We studied renal cell carcinoma (RCC) in comparison to normal (human renal proximal tubule) cells, as a model to better understand the role of CD40 in epithelial cells. CD40 ligation by membrane-presented CD40 ligand (mCD40L), but not soluble CD40 agonist, induced extensive apoptosis in RCC cells; by contrast, normal cells were totally refractory to mCD40L. These findings underline the importance of CD40 ‘signal-quality’ on cell fate and explain the lack of pro-apoptotic effects in RCC cells previously, while confirming the tumour specificity of CD40 in epithelial cells. mCD40L differentially regulated TRAF expression, causing sustained TRAF2/TRAF3 induction in RCC cells, yet downregulation of TRAF2 and no TRAF3 induction in normal cells, observations strikingly reminiscent of TRAF modulation in B-lymphocytes. mCD40L triggered reactive oxygen species (ROS) production, critical in apoptosis, and NADPH oxidase (Nox)-subunit p40phox phosphorylation, with Nox blockade abrogating apoptosis thus implying Nox-dependent initial ROS release. mCD40L mediated downregulation of Thioredoxin-1 (Trx-1), ASK1 phosphorylation, and JNK and p38 activation. Although both JNK/p38 were essential in apoptosis, p38 activation was JNK-dependent, which is the first report of such temporally defined JNK-p38 interplay during an apoptotic programme. CD40-killing entrained Bak/Bax induction, controlled by JNK/p38, and caspase-9-dependent mitochondrial apoptosis, accompanied by pro-inflammatory cytokine secretion, the repertoire of which also depended on CD40 signal quality. Previous reports suggested that, despite the ability of soluble CD40 agonist to reduce RCC tumour size in vivo via immunocyte activation, RCC could be targeted more effectively by combining CD40-mediated immune activation with direct tumour CD40 signalling. Since mCD40L represents a potent tumour cell-specific killing signal, our work not only offers insights into CD40’s biology in normal and malignant epithelial cells, but also provides an avenue for a ‘double-hit’ approach for inflammatory, tumour cell-specific CD40-based therapy.
Type I-F CRISPR-Cas resistance against virulent phages results in abortive infection and provides population-level immunity
Authors: Watson Bridget N. J. , Vercoe Reuben B. , Salmond George P. C. , Westra Edze R. , Staals Raymond H. J , Fineran Peter C.
Published: December 2019

Type I CRISPR-Cas systems are abundant and widespread adaptive immune systems in bacteria and can greatly enhance bacterial survival in the face of phage infection. Upon phage infection, some CRISPR-Cas immune responses result in bacterial dormancy or slowed growth, which suggests the outcomes for infected cells may vary between systems. Here we demonstrate that type I CRISPR immunity of Pectobacterium atrosepticum leads to suppression of two unrelated virulent phages, ɸTE and ɸM1. Immunity results in an abortive infection response, where infected cells do not survive, but viral propagation is severely decreased, resulting in population protection due to the reduced phage epidemic. Our findings challenge the view of CRISPR-Cas as a system that protects the individual cell and supports growing evidence of abortive infection by some types of CRISPR-Cas systems.
Synthesis of higher carboxylic acids from ethers, CO2 and H2
Authors: Wang Ying , Qian Qingli , Zhang Jingjing , Bediako Bernard Baffour Asare , Wang Zhenpeng , Liu Huizhen , Han Buxing
Published: December 2019

Synthesis of higher carboxylic acids using CO2 and H2 is of great importance, because CO2 is an attractive renewable C1 resource and H2 is a cheap and clean reductant. Herein we report a route to produce higher carboxylic acids via reaction of ethers with CO2 and H2. We show that the reaction can be efficiently catalyzed by an IrI4 catalyst with LiI as promoter at 170 °C, 5 MPa of CO2 and 2 MPa of H2. The catalytic system applies to various ether substrates. The mechanistic study indicates that the ethers are converted to olefins, which are further transformed into alkyl iodides. The higher carboxylic acids are produced by carbonylation of alkyl iodides with CO generated in situ via RWGS reaction. This report offers an alternative strategy of higher carboxylic acid synthesis and CO2 transformation.
The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant
Authors: Bogdanow Boris , Wang Xi , Eichelbaum Katrin , Sadewasser Anne , Husic Immanuel , Paki Katharina , Budt Matthias , Hergeselle Martha , Vetter Barbara , Hou Jingyi , Chen Wei , Wiebusch Lüder , Meyer Irmtraud M. , Wolff Thorsten , Selbach Matthias
Published: December 2019

Pandemic influenza A virus (IAV) outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular basis of this species barrier is incompletely understood. Here we combine metabolic pulse labeling and quantitative proteomics to monitor protein synthesis upon infection of human cells with a human- and a bird-adapted IAV strain and observe striking differences in viral protein synthesis. Most importantly, the matrix protein M1 is inefficiently produced by the bird-adapted strain. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Strain-specific M segment splicing is controlled by the 3′ splice site and functionally important for permissive infection. In silico and biochemical evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, we identify M segment RNA splicing as a viral host range determinant.
Cerebral oxygenation during locomotion is modulated by respiration
Authors: Zhang Qingguang , Roche Morgane , Gheres Kyle W. , Chaigneau Emmanuelle , Kedarasetti Ravi T. , Haselden William D. , Charpak Serge , Drew Patrick J.
Published: December 2019

In the brain, increased neural activity is correlated with increases of cerebral blood flow and tissue oxygenation. However, how cerebral oxygen dynamics are controlled in the behaving animal remains unclear. We investigated to what extent cerebral oxygenation varies during locomotion. We measured oxygen levels in the cortex of awake, head-fixed mice during locomotion using polarography, spectroscopy, and two-photon phosphorescence lifetime measurements of oxygen sensors. We find that locomotion significantly and globally increases cerebral oxygenation, specifically in areas involved in locomotion, as well as in the frontal cortex and the olfactory bulb. The oxygenation increase persists when neural activity and functional hyperemia are blocked, occurred both in the tissue and in arteries feeding the brain, and is tightly correlated with respiration rate and the phase of respiration cycle. Thus, breathing rate is a key modulator of cerebral oxygenation and should be monitored during hemodynamic imaging, such as in BOLD fMRI.
Epidemic dynamics of respiratory syncytial virus in current and future climates
Authors: Baker Rachel E. , Mahmud Ayesha S. , Wagner Caroline E. , Yang Wenchang , Pitzer Virginia E. , Viboud Cecile , Vecchi Gabriel A. , Metcalf C. Jessica E. , Grenfell Bryan T.
Published: December 2019

A key question for infectious disease dynamics is the impact of the climate on future burden. Here, we evaluate the climate drivers of respiratory syncytial virus (RSV), an important determinant of disease in young children. We combine a dataset of county-level observations from the US with state-level observations from Mexico, spanning much of the global range of climatological conditions. Using a combination of nonlinear epidemic models with statistical techniques, we find consistent patterns of climate drivers at a continental scale explaining latitudinal differences in the dynamics and timing of local epidemics. Strikingly, estimated effects of precipitation and humidity on transmission mirror prior results for influenza. We couple our model with projections for future climate, to show that temperature-driven increases to humidity may lead to a northward shift in the dynamic patterns observed and that the likelihood of severe outbreaks of RSV hinges on projections for extreme rainfall.
Primary care risk stratification in COPD using routinely collected data: a secondary data analysis
Authors: Johnson Matthew , Rigge Lucy , Culliford David , Josephs Lynn , Thomas Mike , Wilkinson Tom
Published: December 2019

Most clinical contacts with chronic obstructive pulmonary disease (COPD) patients take place in primary care, presenting opportunity for proactive clinical management. Electronic health records could be used to risk stratify diagnosed patients in this setting, but may be limited by poor data quality or completeness. We developed a risk stratification database algorithm using the DOSE index (Dyspnoea, Obstruction, Smoking and Exacerbation) with routinely collected primary care data, aiming to calculate up to three repeated risk scores per patient over five years, each separated by at least one year. Among 10,393 patients with diagnosed COPD, sufficient primary care data were present to calculate at least one risk score for 77.4%, and the maximum of three risk scores for 50.6%. Linked secondary care data revealed primary care under-recording of hospital exacerbations, which translated to a slight, non-significant cohort average risk score reduction, and an understated risk group allocation for less than 1% of patients. Algorithmic calculation of the DOSE index is possible using primary care data, and appears robust to the absence of linked secondary care data, if unavailable. The DOSE index appears a simple and practical means of incorporating risk stratification into the routine primary care of COPD patients, but further research is needed to evaluate its clinical utility in this setting. Although secondary analysis of routinely collected primary care data could benefit clinicians, patients and the health system, standardised data collection and improved data quality and completeness are also needed.
Electrical charge state identification and control for the silicon vacancy in 4H-SiC
Authors: Bathen M. E. , Galeckas A. , Müting J. , Ayedh H. M. , Grossner U. , Coutinho J. , Frodason Y. K. , Vines L.
Published: December 2019

Reliable single-photon emission is crucial for realizing efficient spin-photon entanglement and scalable quantum information systems. The silicon vacancy ($${V}_{{\rm{Si}}}$$VSi) in 4H-SiC is a promising single-photon emitter exhibiting millisecond spin coherence times, but suffers from low photon counts, and only one charge state retains the desired spin and optical properties. Here, we demonstrate that emission from $${V}_{{\rm{Si}}}$$VSi defect ensembles can be enhanced by an order of magnitude via fabrication of Schottky barrier diodes, and sequentially modulated by almost $$50 \%$$50% via application of external bias. Furthermore, we identify charge state transitions of $${V}_{{\rm{Si}}}$$VSi by correlating optical and electrical measurements, and realize selective population of the bright state. Finally, we reveal a pronounced Stark shift of 55 GHz for the V1′ emission line state of $${V}_{{\rm{Si}}}$$VSi at larger electric fields, providing a means to modify the single-photon emission. The approach presented herein paves the way towards obtaining complete control of, and drastically enhanced emission from, $${V}_{{\rm{Si}}}$$VSi defect ensembles in 4H-SiC highly suitable for quantum applications.
Field-induced double spin spiral in a frustrated chiral magnet
Authors: Ramakrishnan Mahesh , Constable Evan , Cano Andres , Mostovoy Maxim , White Jonathan S. , Gurung Namrata , Schierle Enrico , Brion Sophie de , Colin Claire V. , Gay Frederic , Lejay Pascal , Ressouche Eric , Weschke Eugen , Scagnoli Valerio , Ballou Rafik , Simonet Virginie , Staub Urs
Published: December 2019

Magnetic ground states with peculiar spin textures, such as magnetic skyrmions and multifunctional domains are of enormous interest for the fundamental physics governing their origin as well as potential applications in emerging technologies. Of particular interest are multiferroics, where sophisticated interactions between electric and magnetic phenomena can be used to tailor several functionalities. We report the direct observation of a magnetic field induced long-wavelength spin spiral modulation in the chiral compound Ba$${}_{3}$$3TaFe$${}_{3}$$3Si$${}_{2}$$2O$${}_{14}$$14, which emerges out of a helical ground state, and is hallmarked by the onset of a unique chirality-dependent contribution to the bulk electric polarization. The periodicity of the field-induced modulation, several hundreds of nm depending on the field value, is comparable to the length scales of mesoscopic topological defects such as skyrmions, merons, and solitons. The phase transition and observed threshold behavior are consistent with a phenomenology based on the allowed Lifshitz invariants for the chiral symmetry of langasite, which intriguingly contain all the essential ingredients for the realization of topologically stable antiferromagnetic skyrmions. Our findings open up new directions to explore topological correlations of antiferromagnetic spintronic systems based on non-collinear magnetic systems with additional ferroic functionalities.
Differences in lipidome and metabolome organization of prefrontal cortex among human populations
Authors: Tkachev Anna , Stepanova Vita , Zhang Lei , Khrameeva Ekaterina , Zubkov Dmitry , Giavalisco Patrick , Khaitovich Philipp
Published: December 2019

Human populations, despite their overwhelming similarity, contain some distinct phenotypic, genetic, epigenetic, and gene expression features. In this study, we explore population differences at yet another level of molecular phenotype: the abundance of non-polar and polar low molecular weight compounds, lipids and metabolites in the prefrontal cortical region of the brain. We assessed the abundance of 1,670 lipids and 258 metabolites in 146 Han Chinese, 97 Western European, and 60 African American individuals of varying ages, covering most of the lifespan. The statistical analysis and logistic regression models both demonstrated extensive lipid and metabolic divergence of the Han Chinese individuals from the other two populations. This divergence was age-dependent, peaking in young adults, and involved metabolites and lipids clustering in specific metabolic pathways.
Interactions of Ionic Liquids and Spirocyclic Compounds with Liposome Model Membranes. A Steady-State Fluorescence Anisotropy Study
Authors: Rantamäki Antti H. , Chen Wen , Hyväri Paulus , Helminen Jussi , Partl Gabriel , King Alistair W. T. , Wiedmer Susanne K.
Published: December 2019

Understanding the toxicity of ionic liquids (ILs) is crucial in the search of greener chemicals. By comparing in vivo toxicity and in vitro interactions determined between compounds and biomimetic lipid membranes, more detailed toxicity vs. structure relation can be obtained. However, determining the interactions between non-surface-active compounds and liposomes has been a challenging task. Organisational changes induced by ILs and IL-like spirocyclic compounds within 1,6-diphenyl-1,3,5-hexatriene-doped biomimetic liposomes was studied by steady-state fluorescence anisotropy technique. The extent of organisational changes detected within the liposome bilayers were compared to the toxicity of the compounds determined using Vibrio Fischeri bacteria. Four liposome compositions made of pure 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocoline (POPC) and mixtures of POPC, 1-palmitoyl-2-oleyl-sn-glycero-3-phosphoserine (POPS), and cholesterol (Chol) were tested as biomimetic models. Changes observed within the POPC/POPS/Chol 55:20:25 bilayers correlated the best with the toxicity results: ten out of twelve compounds followed the trend of increasing bilayer disorder – increasing toxicity. The study suggests that the toxicity of non-surface-active compounds is dependent on their ability to diffuse into the bilayers. The extent of bilayer’s organisational changes correlates rather well with the toxicity of the compounds. Highly sensitive technique, such as fluorescence anisotropy measurements, is needed for detecting subtle changes within the bilayer structures.
Mitochondrial morphology provides a mechanism for energy buffering at synapses
Authors: Garcia Guadalupe C. , Bartol Thomas M. , Phan Sébastien , Bushong Eric A. , Perkins Guy , Sejnowski Terrence J. , Ellisman Mark H. , Skupin Alexander
Published: December 2019

Mitochondria as the main energy suppliers of eukaryotic cells are highly dynamic organelles that fuse, divide and are transported along the cytoskeleton to ensure cellular energy homeostasis. While these processes are well established, substantial evidence indicates that the internal structure is also highly variable in dependence on metabolic conditions. However, a quantitative mechanistic understanding of how mitochondrial morphology affects energetic states is still elusive. To address this question, we here present an agent-based multiscale model that integrates three-dimensional morphologies from electron microscopy tomography with the molecular dynamics of the main ATP producing components. We apply our modeling approach to mitochondria at the synapse which is the largest energy consumer within the brain. Interestingly, comparing the spatiotemporal simulations with a corresponding space-independent approach, we find minor spatial effects when the system relaxes toward equilibrium but a qualitative difference in fluctuating environments. These results suggest that internal mitochondrial morphology is not only optimized for ATP production but also provides a mechanism for energy buffering and may represent a mechanism for cellular robustness.
A Pre-clinical Animal Model of Secondary Head and Neck Lymphedema
Authors: Daneshgaran Giulia , Lo Andrea Y. , Paik Connie B. , Cooper Michael N. , Sung Cynthia , Jiao Wan , Park Sun Y. , Ni Pauline , Yu Roy P. , Vorobyova Ivetta , Jashashvili Tea , Hong Young-Kwon , Kim Gene H. , Conti Peter S. , Chai Yang , Wong Alex K.
Published: December 2019

Head and neck lymphedema (HNL) is a disfiguring disease affecting over 90% of patients treated for head and neck cancer. Animal models of lymphedema are used to test pharmacologic and microsurgical therapies; however, no animal model for HNL is described in the literature to date. In this study we describe the first reproducible rat model for HNL. Animals were subjected to two surgical protocols: (1) lymphadenectomy plus irradiation; and (2) sham surgery and no irradiation. Head and neck expansion was measured on post-operative days 15, 30 and 60. Magnetic resonance imaging (MRI) was acquired at the same time points. Lymphatic drainage was measured at day 60 via indocyanine green (ICG) lymphography, after which animals were sacrificed for histological analysis. Postsurgical lymphedema was observed 100% of the time. Compared to sham-operated animals, lymphadenectomy animals experienced significantly more head and neck swelling at all timepoints (P < 0.01). Lymphadenectomy animals had significantly slower lymphatic drainage for 6 days post-ICG injection (P < 0.05). Histological analysis of lymphadenectomy animals revealed 83% greater subcutis thickness (P = 0.008), 22% greater collagen deposition (P = 0.001), 110% greater TGFβ1+ cell density (P = 0.04), 1.7-fold increase in TGFβ1 mRNA expression (P = 0.03), and 114% greater T-cell infiltration (P = 0.005) compared to sham-operated animals. In conclusion, animals subjected to complete lymph node dissection and irradiation developed changes consistent with human clinical postsurgical HNL. This was evidenced by significant increase in all head and neck measurements, slower lymphatic drainage, subcutaneous tissue expansion, increased fibrosis, and increased inflammation compared to sham-operated animals.
Photonic topological semimetals in bianisotropic metamaterials
Authors: Yu You-Zhong , Kuo Chih-Yu , Chern Ruey-Lin , Chan C. T.
Published: December 2019

We analyze the photonic topological phases in bianisotropic metamaterials characterized by a chirality tensor with zero trace. We found that the strength of chirality component determines the topological character of the metamaterial. The underlying medium can be considered as a topological semimetal with the nontrivial band gap in the momentum space. The topological properties are described by the spin-orbit Hamiltonians with spin 1 and characterized by the nonzero topological invariants. In particular, photonic quantum Hall states exist when the longitudinal chirality component exceeds the permittivity, whereas photonic quantum spin Hall states are present when the chiral nihility occurs. Considering the dispersion in the frequency domain, the bianisotropic metamaterial is regarded as a photonic Weyl system that supports the Weyl points and Fermi arcs. The topological features are further illustrated with the robust transport of edge states at an irregular boundary of the metamaterial.
NAA at a high concentration promotes efficient plant regeneration via direct somatic embryogenesis and SE-mediated transformation system in Ranunculus sceleratus
Authors: Xu Ke-dong , Wang Wei , Yu De-shui , Li Xiao-li , Chen Jia-min , Feng Bo-jin , Zhao Ya-wen , Cheng Meng-jia , Liu Xin-xin , Li Cheng-wei
Published: December 2019

The novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.
Generation of multi-solitons and noise-like pulses in a high-powered thulium-doped all-fiber ring oscillator
Authors: Voropaev Vasilii , Donodin Aleksandr , Voronets Andrei , Vlasov Dmitrii , Lazarev Vladimir , Tarabrin Mikhail , Krylov Alexander
Published: December 2019

We report a study on the switching of the generation regimes in a high-powered thulium-doped all-fiber ring oscillator that is passively mode-locked with nonlinear polarization evolution technique with different pumping rates and cavity dispersion values. In one experimental setup, switching was observed between the noise-like pulse and the multi-soliton (in the forms of soliton bunches and soliton rain) regimes by the adjustment of the intracavity polarization controllers. We attributed this to the crucial influence of the nonlinear polarization evolution strength determined by such key parameters as saturation (over-rotation) power, linear phase bias, and nonlinear losses on the pulse evolution and stability. So the soliton collapse effect (leading to noise-like pulse generation) or the peak power clamping effect (generating a bunch of loosely-bound solitons) may determine pulse dynamics. Both the spectrum bandwidth and coherence time were studied for noise-like pulses by varying the cavity length and pump power, as well as the duration of solitons composing bunches. As a result, both noise-like pulses (with spectrum as broad as 32 nm bandwidth) and multi-soliton formations (with individual pulse-widths ranging from 748 to 1273 fs with a cavity length increase from 12 to 53 m) with up to 730 mW average power were generated at a wavelength of around 1.9 μm. The results are important for the realization of the broadband and smooth supercontinuum which can be used as a source for mid-IR vibrational spectroscopy of gas samples for breath analysis and environmental sensing.
Coherent resonance in the distributed cortical network during sensory information processing
Authors: Pisarchik Alexander N. , Maksimenko Vladimir A. , Andreev Andrey V. , Frolov Nikita S. , Makarov Vladimir V. , Zhuravlev Maxim O. , Runnova Anastasija E. , Hramov Alexander E.
Published: December 2019

Neuronal brain network is a distributed computing system, whose architecture is dynamically adjusted to provide optimal performance of sensory processing. A small amount of visual information needed effortlessly be processed, activates neural activity in occipital and parietal areas. Conversely, a visual task which requires sustained attention to process a large amount of sensory information, involves a set of long-distance connections between parietal and frontal areas coordinating the activity of these distant brain regions. We demonstrate that while neural interactions result in coherence, the strongest connection is achieved through coherence resonance induced by adjusting intrinsic brain noise.
Comprehensive multivariate correlations between climatic effect, metabolite-profile, antioxidant capacity and antibacterial activity of Brazilian red propolis metabolites during seasonal study
Authors: do Nascimento Ticiano Gomes , dos Santos Arruda Rodolfo Elleson , da Cruz Almeida Erika Tayse , dos Santos Oliveira José Marcos , Basílio-Júnior Irinaldo Diniz , Celerino de Moraes Porto Isabel Cristina , Rodrigues Sabino Adilson , Tonholo Josealdo , Gray Alexander , Ebel RuAngelie Edrada , Clements Carol , Zhang Tong , Watson David George
Published: December 2019

The standardization of apiceutical products like as propolis extracts has been widely debated worldwide and variations in the propolis chemical composition are still very relevant topics for use-standardized of different propolis-type as medication by much of the world’s population. The present manuscript discuss important issues related to the climate effect and variations in propolis metabolite-profiling changes, antioxidant capacity and variations of the antibacterial activity of the Brazilian red propolis metabolites using comprehensive multivariate correlations. It was observed the increasing of guttiferones concentrations during the intense drought period and drastic decreasing in rainy period. The climate variation induced the high concentration of flavonoids in rainy period with pronounced dropped in some rainy months. The Pearson´s analysis demonstrated correlation between IC50 from DPPH and guttiferones and flavonoids concentrations. The PCA-X and Hotelling T2 test showed outliers during the months with lowest concentrations of formononetin and isoliquiritigenin was observed in antibacterial tests. The PLS-DA, OPLS-DA and VIP analysis demonstrate guttiferone E, guttiferone B, liquiritigenin, naringenin are considered important substances responsible by anti-staphylococcal activity in red propolis composition during the rainy season and drought period, but a synergistic effect with other flavonoids and isoflavonoids are not ruled out.
Hardening and Strain Localisation in Helium-Ion-Implanted Tungsten
Authors: Das Suchandrima , Yu Hongbing , Tarleton Edmund , Hofmann Felix
Published: December 2019

Tungsten is the main candidate material for plasma-facing armour components in future fusion reactors. In-service, fusion neutron irradiation creates lattice defects through collision cascades. Helium, injected from plasma, aggravates damage by increasing defect retention. Both can be mimicked using helium-ion-implantation. In a recent study on 3000 appm helium-implanted tungsten (W-3000He), we hypothesized helium-induced irradiation hardening, followed by softening during deformation. The hypothesis was founded on observations of large increase in hardness, substantial pile-up and slip-step formation around nano-indents and Laue diffraction measurements of localised deformation underlying indents. Here we test this hypothesis by implementing it in a crystal plasticity finite element (CPFE) formulation, simulating nano-indentation in W-3000He at 300 K. The model considers thermally-activated dislocation glide through helium-defect obstacles, whose barrier strength is derived as a function of defect concentration and morphology. Only one fitting parameter is used for the simulated helium-implanted tungsten; defect removal rate. The simulation captures the localised large pile-up remarkably well and predicts confined fields of lattice distortions and geometrically necessary dislocation underlying indents which agree quantitatively with previous Laue measurements. Strain localisation is further confirmed through high resolution electron backscatter diffraction and transmission electron microscopy measurements on cross-section lift-outs from centre of nano-indents in W-3000He.
CD105 (Endoglin) as negative prognostic factor in AML
Authors: Kauer Joseph , Schwartz Karolin , Tandler Claudia , Hinterleitner Clemens , Roerden Malte , Jung Gundram , Salih Helmut R. , Heitmann Jonas S. , Märklin Melanie
Published: December 2019

While several genetic and morphological markers are established and serve to guide therapy of acute myeloid leukaemia (AML), there is still profound need to identify additional markers to better stratify patients. CD105 (Endoglin) is a type I transmembrane protein reported to induce activation and proliferation of endothelial cells. In addition, CD105 is expressed in haematological malignancies and the vessels of solid tumours. Here, CD105 associates with unfavourable disease course, but so far no data are available on the prognostic relevance of CD105 in haematological malignancies. We here generated a novel CD105 antibody for analysis of expression and prognostic relevance of CD105 in a cohort of 62 AML patients. Flow cytometric analysis revealed substantial expression in the various AML FAB types, with FAB M3 type displaying significantly lower surface levels. Next we established a cut-off specific fluorescence level of 5.22 using receiver-operating characteristics, which allowed to group patients in cases with CD105loand CD105hisurface expression and revealed that high CD105 expression correlated significantly with poor overall and progression free survival. In conclusion, we here identify CD105 expression as a novel prognostic marker in AML, which may serve to optimize follow up and treatment decisions for AML patients.
Transcriptomic responses in mouse blood during the first week after in vivo gamma irradiation
Authors: Paul Sunirmal , Kleiman Norman J. , Amundson Sally A.
Published: December 2019

Due to limitations of available human models for development of gene expression based radiation biodosimetry, many such studies have made use of mouse models. To provide a broad view of the gene expression response to irradiation in the mouse, we have exposed male C57BL/6 mice to 0, 1.5, 3, 6 or 10 Gy of gamma rays, sacrificing groups of the mice at 1, 2, 3, 5, or 7 days after exposure. We then profiled global gene expression in blood from individual mice using Agilent microarrays. In general, we found increasing numbers of genes differentially expressed with increasing dose, with more prolonged responses after the higher doses. Gene ontology analysis showed a similar pattern, with more biological processes enriched among the genes responding to higher doses, and at later times after exposure. Clustering the timecourse expression data using maSigPro identified four broad patterns of response, representing different gene ontology functions. The largest of these clusters included genes with initially decreased expression followed by increased expression at later times, a pattern of expression previously reported for several genes following neutron exposure. Another gene cluster showing consistent down regulation suggests genes useful for biodosimetry throughout the first week after exposure can be identified.