bluuebunny/crossref_metadata_2025 huggingface dataset:
A Major Collapse of Kangerlussuaq Glacier's Ice Tongue Between 1932 and 1933 in East Greenland
Authors: Vermassen Flor , Bjørk Anders A. , Sicre Marie‐Alexandrine , Jaeger John M. , Wangner David J. , Kjeldsen Kristian K. , Siggaard‐Andersen Marie‐Louise , Klein Vincent , Mouginot Jeremie , Kjær Kurt H. , Andresen Camilla S.
Published: January 2020

In recent years, several large outlet glaciers in Greenland lost their floating ice tongue, yet little is known regarding their stability over a longer timescale. Here we compile historical documents to demonstrate a major ice tongue collapse of Kangerlussuaq Glacier between 1932 and 1933. This event resulted in a 9‐km retreat, exceeding any of the glacier's recent major retreat events. Sediment cores from the fjord are used to reconstruct sea surface temperatures and to investigate a potential sedimentological trace of the collapse. During the 1920s, local and regional sea surface temperatures and air temperatures increased rapidly, suggesting a climatic trigger for the collapse. Fjord bathymetry played an important role too, as the (partially) pinned ice tongue retreated off a submarine moraine during the event. This historical analogue of a glacier tongue collapse emphasizes the fragility of remaining ice tongues in North Greenland within a warming climate.
Westward Acceleration of Tropical Stratopause Zonal Winds During Major Sudden Stratospheric Warming Events
Authors: Koushik N. , Kumar Karanam Kishore , Siddiqui Tarique A.
Published: January 2020

The tropical Mesosphere‐Lower Thermosphere‐Ionosphere system is found to show significant variabilities during Sudden Stratospheric Warming (SSW) events. Recent studies have highlighted the possible role played by modified background wind conditions in communicating the SSW‐induced stratospheric perturbations to the Mesosphere‐Lower Thermosphere‐Ionosphere region. In the present study, changes in the background zonal winds at the tropical stratopause during major SSW events inferred from MERRA‐2 reanalysis data sets, rocket observations, and model simulations are reported for the first time. The tropical stratopause shows enhanced westward winds during the course of major SSW events. Rocketsonde observations from a low latitude station Thumba (8.5 ° N,76.9 ° E) also showed significant westward acceleration during three major SSW events. Further, Specified Dynamics version of the Whole Atmosphere Community Climate Model simulations for the 2008–2009 SSW replicate the observed features.
Systematic Bias in the Prediction of Warm‐Rain Hydrometeors in the WDM6 Microphysics Scheme and Modifications
Authors: Lei Hengchi , Guo Jiaxu , Chen Di , Yang Jiefan
Published: January 2020

Modifications are made to the calculation of warm‐rain hydrometeor number concentrations of the Weather Research and Forecasting double‐moment six‐class (WDM6) microphysics scheme. These modifications are related with cloud condensation nuclei activation, cloud droplet evaporation, and snow and graupel melting. The effects of the modifications are tested in a North China heavy rain event (Case01) as well as a short‐duration rain event in Hebei Province of China (Case02). The results show that the WDM6 scheme underestimates the cloud mixing ratios (Qc) and number concentrations (Nc), while it overestimates the rain mixing ratios (Qr) and number concentrations (Nr). Meanwhile, the WDM6 scheme overestimates the mass mean diameter of cloud droplets (Dmc) and underestimates that of raindrops (Dmr). Through microphysical budget analysis, it is found that the inappropriate calculations of cloud condensation nuclei activation and cloud evaporation are responsible for the underestimation of Nc and larger Dmc. The overestimation of the autoconversion rate resulting from larger Dmc plays a decisive role in the overestimation of Qr and Nr, as well as in the underestimation of Qc. The overestimation of raindrops produced by the melting of snow and graupel is another reason for higher Qr and Nr. By comparing with the airborne observations in Case02, it is found that the Nc and Dmc simulation are notably improved with the direct modifications of Nc. The Nr simulation is closer to the observation after the melting of snow and graupel are modified.
The Sources and Atmospheric Pathway of Phosphorus to a High Alpine Forest in Eastern Tibetan Plateau, China
Authors: Meng Ya , Li Rui , Fu Hongbo , Bing Haijian , Huang Kan , Wu Yanhong
Published: January 2020

Atmospheric deposition is considered as an important source of phosphorus (P) to P‐limited ecosystems. The PM2.5 samples were collected from a high alpine P‐limited forest of Gongga Mountain (Mt. Gongga), eastern Tibetan Plateau from May 2015 to May 2016. Total P (TP) exhibited a higher concentration in the dry season (November to April, 96 ± 30 ng/m3) than that in the wet season (May to October, 77 ± 21 ng/m3). Source apportionment exhibited that 22% and 44% of TP in the dry season were contributed by soil dust and biomass burning, respectively. During the wet season, soil dust, biomass burning, and anthropogenic sources were estimated to contribute to 19%, 26%, and 41% of TP, respectively. Dissolved organic P (DOP) was found to be the significant fraction of total dissolved P (TDP), accounting for 65% and 53% of TDP in the dry and wet season, respectively. The significant correlations between DOP and KBB+ suggested that the soluble P originating from biomass burning was possible mainly in the form of DOP. In addition, the acidification of apatite during the transport could explain the dissolved inorganic P level in the wet season. Supposing that all the soluble P was bioavailable, the atmospheric deposition of TDP was estimated to result in a fixation of 0.1394 kg C/m2/yr, accounting for 23% of net primary productivity in a forest of Mt. Gongga. The data showed herein highlighted the importance of atmospheric dry deposition of P to the long‐term fertility of high‐elevation soils.
A Unified Data‐Driven Method to Derive Hydrologic Dynamics From Global SMAP Surface Soil Moisture and GPM Precipitation Data
Authors: Mao Yixin , Crow Wade T. , Nijssen Bart
Published: January 2020

Data sets provided by the Soil Moisture Active Passive (SMAP) and the Global Precipitation Measurement (GPM) satellite missions contain rich information about land surface hydrologic processes.In this study, a unified regression method is proposed and applied to these global data sets to investigate surface soil moisture (SSM) dynamics. Two forms of regressors are implemented: 1) the linear regressors of SSM and precipitation flux and 2) the linear regressors of SSM and precipitation flux with an additional interaction term. Regression results based on 3 years of global SMAP and GPM data show that the unified regression method can identify the SSM characteristics found by several recent studies, including the SSM exponential decay rate, the fraction of precipitation retained in the surface soil layer, and the effective depth of hydrologic storage. Additionally, including the interaction regressor provides a novel way to derive the sensitivity of infiltration/runoff partitioning to antecedent SSM without the need for streamflow observations. These SMAP/GPM regression results are compared with those derived from a global SSM data set simulated by the variable infiltration capacity model. Relative to the satellite data, variable infiltration capacity retains moisture longer in the top layer, retains too much precipitation input in that layer, and exhibits levels of sensitivity of runoff/infiltration partitioning to top‐layer soil moisture that generally match SMAP especially in humid regions. This study demonstrates that the regression‐based method can recover useful process‐level insight from SMAP SSM retrievals and is a viable tool for evaluating the representation of surface processes in hydrologic models.
A Universal Model of Unsaturated Hydraulic Conductivity With Complementary Adsorptive and Diffusive Process Components
Authors: Modaresi Rad Arash , Ghahraman Bijan , Mosaedi Abolfazl , Sadegh Mojtaba
Published: January 2020

Accurate estimation of unsaturated hydraulic conductivity (HC) is one of the most challenging problems in soil science. Here, we propose a novel approach to model HC using percolation theory. Transient behavior of water transport phenomena at low moisture contents requires additional physical process representation, beside capillary conductivity, to ensure accurate prediction of unsaturated HC. We augment the capillary model from percolation theory with two additional components, namely, (1) film flow, which is the product of volumetric flow rate per perimeter by specific perimeter of solid particles, and (2) isothermal vapor HC, derived from the Fick's law of vapor diffusion and relative humidity. The fractal characteristics of last fractal regime are used to model tortuosity and ultimately HC of vapor flow. Since the typical pressure head range of universal scaling from percolation theory is analogous to the range of vapor flow, we demonstrate that the universal scaling presented in previous studies is not sufficient to model HC for water contents below a crossover point. We also, by analyzing the scaled water retention properties, demonstrate that most studied soils exhibit three fractal regimes. Therefore, a piecewise HC function of capillary flow is developed to account for three fractal regimes, providing more flexibility for soils with multimodal characteristics. The proposed joint HC function is more accurate compared to the model of Peters‐Durner‐Iden and predecessor percolation theory models.
The gut microbiota response to helminth infection depends on host sex and genotype
Authors: Ling Fei , Steinel Natalie , Weber Jesse , Ma Lei , Smith Chris , Correa Decio , Zhu Bin , Bolnick Daniel , Wang Gaoxue
Published: January 2020

Vertebrates’ gut microbial communities can be altered by the hosts’ parasites. Helminths inhabiting the gut lumen can interact directly with their host’s microbiota via physical contact, chemical products, or competition for nutrients. Indirect interactions can also occur, for instance when helminths induce or suppress host immunity in ways that have collateral effects on the microbiota. If there is genetic variation in host immune responses to parasites, we would expect such indirect effects to be conditional on host genotype. To test for such genotype by infection interactions, we experimentally exposed Gasterosteus aculeatus to their naturally co-evolved parasite, Schistocephalus solidus. The host microbiota differed in response to parasite exposure, and between infected and uninfected fish. The magnitude and direction of microbial responses to infection differed between host sexes, and also differed between variants at autosomal quantitative trait loci. These results indicate that host genotype and sex regulate the effect of helminth infection on a vertebrate gut microbiota. If this result holds in other taxa, especially humans, then helminth-based therapeutics for dysbiosis might need to be tailored to host genotype and sex.
Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice
Authors: Keipert Susanne , Lutter Dominik , Schroeder Bjoern O. , Brandt Daniel , Ståhlman Marcus , Schwarzmayr Thomas , Graf Elisabeth , Fuchs Helmut , de Angelis Martin Hrabe , Tschöp Matthias H. , Rozman Jan , Jastroch Martin
Published: January 2020

Uncoupling protein 1 (UCP1) executes thermogenesis in brown adipose tissue, which is a major focus of human obesity research. Although the UCP1-knockout (UCP1 KO) mouse represents the most frequently applied animal model to judge the anti-obesity effects of UCP1, the assessment is confounded by unknown anti-obesity factors causing paradoxical obesity resistance below thermoneutral temperatures. Here we identify the enigmatic factor as endogenous FGF21, which is primarily mediating obesity resistance. The generation of UCP1/FGF21 double-knockout mice (dKO) fully reverses obesity resistance. Within mild differences in energy metabolism, urine metabolomics uncover increased secretion of acyl-carnitines in UCP1 KOs, suggesting metabolic reprogramming. Strikingly, transcriptomics of metabolically important organs reveal enhanced lipid and oxidative metabolism in specifically white adipose tissue that is fully reversed in dKO mice. Collectively, this study characterizes the effects of endogenous FGF21 that acts as master regulator to protect from diet-induced obesity in the absence of UCP1.
Millimeters long super flexible Mn5Si3@SiO2 electrical nanocables applicable in harsh environments
Authors: Sun Yong , Sun Bo , He Jingbo , Yang Guowei , Wang Chengxin
Published: January 2020

Providing high performance electrical nano-interconnects for micro-nano electronics that are robust in harsh environments is highly demanded. Today, electrical nano-interconnects based on metallic nanowires, e.g. Ag and Cu, are limited by their positive physicochemical reactivity and ductility under large strain (i.e. irreversible dislocations and local necking-down elongation) at high temperatures or in strong oxidizing and acidic environments. Herein, to overcome these limitations, high-quality millimetre-sized soft manganese-based silicide (Mn5Si3@SiO2) nanowire nanocables are designed via a glassy Si–Mn–O matrix assisted growth. The proposed nanocables exhibit good electrical performance (resistivity of 1.28 to 3.84×10-6 Ωm and maximum current density 1.22 to 3.54×107 A cm−2) at temperatures higher than 317°C in air atmosphere, strongly acidic (HCl, PH=1.0) and oxidizing (H2O2, 10%) ambient, and under complex electric field. The proposed Mn5Si3@SiO2 nanocables, which withstand a strain of 16.7% free of failure, could be exploited for diverse applications in flexible electronics and complex wiring configurations.
Insight into dynamic and steady-state active sites for nitrogen activation to ammonia by cobalt-based catalyst
Authors: Wang Xiuyun , Peng Xuanbei , Chen Wei , Liu Guangyong , Zheng Anmin , Zheng Lirong , Ni Jun , Au Chak-tong , Jiang Lilong
Published: January 2020

The industrial synthesis of ammonia (NH3) using iron-based Haber-Bosch catalyst requires harsh reaction conditions. Developing advanced catalysts that perform well at mild conditions (<400 °C, <2 MPa) for industrial application is a long-term goal. Here we report a Co-N-C catalyst with high NH3 synthesis rate that simultaneously exhibits dynamic and steady-state active sites. Our studies demonstrate that the atomically dispersed cobalt weakly coordinated with pyridine N reacts with surface H2 to produce NH3 via a chemical looping pathway. Pyrrolic N serves as an anchor to stabilize the single cobalt atom in the form of Co1-N3.5 that facilitates N2 adsorption and step-by-step hydrogenation of N2 to *HNNH, *NH-NH3 and *NH2-NH4. Finally, NH3 is facilely generated via the breaking of the *NH2-NH4 bond. With the co-existence of dynamic and steady-state single atom active sites, the Co-N-C catalyst circumvents the bottleneck of N2 dissociation, making the synthesis of NH3 at mild conditions possible.
Decoding quantum errors with subspace expansions
Authors: McClean Jarrod R. , Jiang Zhang , Rubin Nicholas C. , Babbush Ryan , Neven Hartmut
Published: January 2020

With rapid developments in quantum hardware comes a push towards the first practical applications. While fully fault-tolerant quantum computers are not yet realized, there may exist intermediate forms of error correction that enable practical applications. In this work, we consider the idea of post-processing error decoders using existing quantum codes, which mitigate errors on logical qubits using post-processing without explicit syndrome measurements or additional qubits beyond the encoding overhead. This greatly simplifies the experimental exploration of quantum codes on real, near-term devices, removing the need for locality of syndromes or fast feed-forward. We develop the theory of the method and demonstrate it on an example with the perfect [[5, 1, 3]] code, which exhibits a pseudo-threshold of p ≈ 0.50 under a single qubit depolarizing channel applied to all qubits. We also provide a demonstration of improved performance on an unencoded hydrogen molecule.
Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G
Authors: Yang Hanjing , Ito Fumiaki , Wolfe Aaron D. , Li Shuxing , Mohammadzadeh Nazanin , Love Robin P. , Yan Maocai , Zirkle Brett , Gaba Amit , Chelico Linda , Chen Xiaojiang S.
Published: January 2020

APOBEC3G, a member of the double-domain cytidine deaminase (CD) APOBEC, binds RNA to package into virions and restrict HIV-1 through deamination-dependent or deamination-independent inhibition. Mainly due to lack of a full-length double-domain APOBEC structure, it is unknown how CD1/CD2 domains connect and how dimerization/multimerization is linked to RNA binding and virion packaging for HIV-1 restriction. We report rhesus macaque A3G structures that show different inter-domain packing through a short linker and refolding of CD2. The A3G dimer structure has a hydrophobic dimer-interface matching with that of the previously reported CD1 structure. A3G dimerization generates a surface with intensified positive electrostatic potentials (PEP) for RNA binding and dimer stabilization. Unexpectedly, mutating the PEP surface and the hydrophobic interface of A3G does not abolish virion packaging and HIV-1 restriction. The data support a model in which only one RNA-binding mode is critical for virion packaging and restriction of HIV-1 by A3G.
Possible Luttinger liquid behavior of edge transport in monolayer transition metal dichalcogenide crystals
Authors: Yang Guanhua , Shao Yan , Niu Jiebin , Ma Xiaolei , Lu Congyan , Wei Wei , Chuai Xichen , Wang Jiawei , Cao Jingchen , Huang Hao , Xu Guangwei , Shi Xuewen , Ji Zhuoyu , Lu Nianduan , Geng Di , Qi Jing , Cao Yun , Liu Zhongliu , Liu Liwei , Huang Yuan , Liao Lei , Dang Weiqi , Zhang Zhengwei , Liu Yuan , Duan Xidong , Chen Jiezhi , Fan Zhiqiang , Jiang Xiangwei , Wang Yeliang , Li Ling , Gao Hong-Jun , Duan Xiangfeng , Liu Ming
Published: January 2020

In atomically-thin two-dimensional (2D) semiconductors, the nonuniformity in current flow due to its edge states may alter and even dictate the charge transport properties of the entire device. However, the influence of the edge states on electrical transport in 2D materials has not been sufficiently explored to date. Here, we systematically quantify the edge state contribution to electrical transport in monolayer MoS2/WSe2 field-effect transistors, revealing that the charge transport at low temperature is dominated by the edge conduction with the nonlinear behavior. The metallic edge states are revealed by scanning probe microscopy, scanning Kelvin probe force microscopy and first-principle calculations. Further analyses demonstrate that the edge-state dominated nonlinear transport shows a universal power-law scaling relationship with both temperature and bias voltage, which can be well explained by the 1D Luttinger liquid theory. These findings demonstrate the Luttinger liquid behavior in 2D materials and offer important insights into designing 2D electronics.
Tissue mechanics drives regeneration of a mucociliated epidermis on the surface of Xenopus embryonic aggregates
Authors: Kim Hye Young , Jackson Timothy R. , Stuckenholz Carsten , Davidson Lance A.
Published: January 2020

Injury, surgery, and disease often disrupt tissues and it is the process of regeneration that aids the restoration of architecture and function. Regeneration can occur through multiple strategies including stem cell expansion, transdifferentiation, or proliferation of differentiated cells. We have identified a case of regeneration in Xenopus embryonic aggregates that restores a mucociliated epithelium from mesenchymal cells. Following disruption of embryonic tissue architecture and assembly of a compact mesenchymal aggregate, regeneration first restores an epithelium, transitioning from mesenchymal cells at the surface of the aggregate. Cells establish apico-basal polarity within 5 hours and a mucociliated epithelium within 24 hours. Regeneration coincides with nuclear translocation of the putative mechanotransducer YAP1 and a sharp increase in aggregate stiffness, and regeneration can be controlled by altering stiffness. We propose that regeneration of a mucociliated epithelium occurs in response to biophysical cues sensed by newly exposed cells on the surface of a disrupted mesenchymal tissue.
Fast temporal dynamics and causal relevance of face processing in the human temporal cortex
Authors: Schrouff Jessica , Raccah Omri , Baek Sori , Rangarajan Vinitha , Salehi Sina , Mourão-Miranda Janaina , Helili Zeinab , Daitch Amy L. , Parvizi Josef
Published: January 2020

We measured the fast temporal dynamics of face processing simultaneously across the human temporal cortex (TC) using intracranial recordings in eight participants. We found sites with selective responses to faces clustered in the ventral TC, which responded increasingly strongly to marine animal, bird, mammal, and human faces. Both face-selective and face-active but non-selective sites showed a posterior to anterior gradient in response time and selectivity. A sparse model focusing on information from the human face-selective sites performed as well as, or better than, anatomically distributed models when discriminating faces from non-faces stimuli. Additionally, we identified the posterior fusiform site (pFUS) as causally the most relevant node for inducing distortion of conscious face processing by direct electrical stimulation. These findings support anatomically discrete but temporally distributed response profiles in the human brain and provide a new common ground for unifying the seemingly contradictory modular and distributed modes of face processing.
Expanding the genome-targeting scope and the site selectivity of high-precision base editors
Authors: Tan Junjie , Zhang Fei , Karcher Daniel , Bock Ralph
Published: January 2020

Base editors (BEs) are RNA-guided CRISPR-Cas-derived genome editing tools that induce single-nucleotide changes. The limitations of current BEs lie in their low precision (especially when multiple target nucleotides of the deaminase are present within the activity window) and their restriction to targets that are in proper distance from the PAM sequence. We have recently developed high-precision cytidine BEs by engineering CDA1 truncations and nCas9 fusions that predominantly edit nucleotide C−18 relative to the PAM sequence NGG. Here, by testing fusions with Cas9 variants that recognize alternative PAMs, we provide a series of high-precision BEs that greatly expand the versatility of base editing. In addition, we obtained BEs that selectively edit C−15 or C−16. We also show that our high-precision BEs can substantially reduce off-target effect. These improved base editing tools will be widely applicable in basic research, biotechnology and gene therapy.
Spatial quantification of dynamic inter and intra particle crystallographic heterogeneities within lithium ion electrodes
Authors: Finegan Donal P. , Vamvakeros Antonis , Tan Chun , Heenan Thomas M. M. , Daemi Sohrab R. , Seitzman Natalie , Di Michiel Marco , Jacques Simon , Beale Andrew M. , Brett Dan J. L. , Shearing Paul R. , Smith Kandler
Published: January 2020

The performance of lithium ion electrodes is hindered by unfavorable chemical heterogeneities that pre-exist or develop during operation. Time-resolved spatial descriptions are needed to understand the link between such heterogeneities and a cell’s performance. Here, operando high-resolution X-ray diffraction-computed tomography is used to spatially and temporally quantify crystallographic heterogeneities within and between particles throughout both fresh and degraded LixMn2O4 electrodes. This imaging technique facilitates identification of stoichiometric differences between particles and stoichiometric gradients and phase heterogeneities within particles. Through radial quantification of phase fractions, the response of distinct particles to lithiation is found to vary; most particles contain localized regions that transition to rock salt LiMnO2 within the first cycle. Other particles contain monoclinic Li2MnO3 near the surface and almost pure spinel LixMn2O4 near the core. Following 150 cycles, concentrations of LiMnO2 and Li2MnO3 significantly increase and widely vary between particles.
Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy
Authors: Sharma Meenu , Khong Hiep , Fa’ak Faisal , Bentebibel Salah-Eddine , Janssen Louise M. E. , Chesson Brent C. , Creasy Caitlin A. , Forget Marie-Andrée , Kahn Laura Maria S. , Pazdrak Barbara , Karki Binisha , Hailemichael Yared , Singh Manisha , Vianden Christina , Vennam Srinivas , Bharadwaj Uddalak , Tweardy David J. , Haymaker Cara , Bernatchez Chantale , Huang Shixia , Rajapakshe Kimal , Coarfa Cristian , Hurwitz Michael E. , Sznol Mario , Hwu Patrick , Hoch Ute , Addepalli Murali , Charych Deborah H. , Zalevsky Jonathan , Diab Adi , Overwijk Willem W.
Published: January 2020

High dose interleukin-2 (IL-2) is active against metastatic melanoma and renal cell carcinoma, but treatment-associated toxicity and expansion of suppressive regulatory T cells (Tregs) limit its use in patients with cancer. Bempegaldesleukin (NKTR-214) is an engineered IL-2 cytokine prodrug that provides sustained activation of the IL-2 pathway with a bias to the IL-2 receptor CD122 (IL-2Rβ). Here we assess the therapeutic impact and mechanism of action of NKTR-214 in combination with anti-PD-1 and anti-CTLA-4 checkpoint blockade therapy or peptide-based vaccination in mice. NKTR-214 shows superior anti-tumor activity over native IL-2 and systemically expands anti-tumor CD8+T cells while inducing Treg depletion in tumor tissue but not in the periphery. Similar trends of intratumoral Treg dynamics are observed in a small cohort of patients treated with NKTR-214. Mechanistically, intratumoral Treg depletion is mediated by CD8+Teff-associated cytokines IFN-γ and TNF-α. These findings demonstrate that NKTR-214 synergizes with T cell-mediated anti-cancer therapies.
Non-invasive recording from the human olfactory bulb
Authors: Iravani Behzad , Arshamian Artin , Ohla Kathrin , Wilson Donald A. , Lundström Johan N.
Published: January 2020

Current non-invasive neuroimaging methods can assess neural activity in all areas of the human brain but the olfactory bulb (OB). The OB has been suggested to fulfill a role comparable to that of V1 and the thalamus in the visual system and have been closely linked to a wide range of olfactory tasks and neuropathologies. Here we present a method for non-invasive recording of signals from the human OB with millisecond precision. We demonstrate that signals obtained via recordings from EEG electrodes at the nasal bridge represent responses from the human olfactory bulb - recordings we term Electrobulbogram (EBG). The EBG will aid future olfactory-related translational work but can also potentially be implemented as an everyday clinical tool to detect pathology-related changes in human central olfactory processing in neurodegenerative diseases. In conclusion, the EBG is localized to the OB, is reliable, and follows response patterns demonstrated in non-human animal models.
Pollution exacerbates China’s water scarcity and its regional inequality
Authors: Ma Ting , Sun Siao , Fu Guangtao , Hall Jim W. , Ni Yong , He Lihuan , Yi Jiawei , Zhao Na , Du Yunyan , Pei Tao , Cheng Weiming , Song Ci , Fang Chuanglin , Zhou Chenghu
Published: January 2020

Inadequate water quality can mean that water is unsuitable for a variety of human uses, thus exacerbating freshwater scarcity. Previous large-scale water scarcity assessments mostly focused on the availability of sufficient freshwater quantity for providing supplies, but neglected the quality constraints on water usability. Here we report a comprehensive nationwide water scarcity assessment in China, which explicitly includes quality requirements for human water uses. We highlight the necessity of incorporating water scarcity assessment at multiple temporal and geographic scales. Our results show that inadequate water quality exacerbates China’s water scarcity, which is unevenly distributed across the country. North China often suffers water scarcity throughout the year, whereas South China, despite sufficient quantities, experiences seasonal water scarcity due to inadequate quality. Over half of the population are affected by water scarcity, pointing to an urgent need for improving freshwater quantity and quality management to cope with water scarcity.
Author Correction: Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages
Authors: Siranosian Benjamin A. , Tamburini Fiona B. , Sherlock Gavin , Bhatt Ami S.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Vaccination with virosomally formulated recombinant CyRPA elicits protective antibodies against Plasmodium falciparum parasites in preclinical in vitro and in vivo models
Authors: Tamborrini Marco , Hauser Julia , Schäfer Anja , Amacker Mario , Favuzza Paola , Kyungtak Kwak , Fleury Sylvain , Pluschke Gerd
Published: January 2020

The Plasmodium falciparum (Pf) cysteine-rich protective antigen (PfCyRPA) has emerged as a promising blood-stage candidate antigen for inclusion into a broadly cross-reactive malaria vaccine. This highly conserved protein among various geographical strains plays a key role in the red blood cell invasion process by P. falciparum merozoites, and antibodies against PfCyRPA can efficiently prevent the entry of the malaria parasites into red blood cells. The aim of the present study was to develop a human-compatible formulation of the PfCyRPA vaccine candidate and confirming its activity in preclinical studies. Recombinant PfCyRPA expressed in HEK 293 cells was chemically coupled to phosphoethanolamine and then incorporated into the membrane of unadjuvanted influenza virosomes approved as antigen delivery system for humans. Laboratory animals were immunised with the virosome-based PfCyRPA vaccine to determine its immunogenic properties and in particular, its capacity to elicit parasite binding and growth-inhibitory antibodies. The vaccine elicited in mice and rabbits high titers of PfCyRPA-specific antibodies that bound to the blood-stage parasites. At a concentration of 10 mg/mL, purified total serum IgG from immunised rabbits inhibited parasite growth in vitro by about 80%. Furthermore, in a P. falciparum infection mouse model, passive transfer of 10 mg of purified total IgG from PfCyRPA vaccinated rabbits reduced the in vivo parasite load by 77%. Influenza virosomes thus represent a suitable antigen delivery system for the induction of protective antibodies against the recombinant PfCyRPA, designating it as a highly suitable component for inclusion into a multivalent and multi-stage virosomal malaria vaccine.
Preventing peripheral intravenous catheter failure by reducing mechanical irritation
Authors: Takahashi Toshiaki , Murayama Ryoko , Abe-Doi Mari , Miyahara-Kaneko Maki , Kanno Chiho , Nakamura Miwa , Mizuno Mariko , Komiyama Chieko , Sanada Hiromi
Published: January 2020

Peripheral intravenous catheter failure is a significant concern in the clinical setting. We investigated the effectiveness of care protocols, including an ultrasonographic “pre-scan” for selecting a large-diameter vein before catheterization, a “post-scan” for confirming the catheter tip position after catheterization with ultrasonography, and the use of a flexible polyurethane catheter to reduce the mechanical irritation that contributes to the incidence of catheter failure. This intervention study was a non-randomized controlled trial to investigate the effectiveness of the abovementioned care protocols, the effects of which were compared to the outcomes in the control group, which received conventional care. For both groups, participants were selected from patients in two wards at the University of Tokyo in Japan between July and November 2017. Inverse probability score-based weighted methods (IPW) using propensity score were used to estimate the effectiveness of care protocols. The primary outcome was catheter failure, which was defined as accidental and unplanned catheter removal. We used Kaplan-Meier survival curves to compare rates of time until catheter failure. We analysed 189 and 233 catheters in the intervention and control groups, respectively. In the control group, 68 catheters (29.2%) were determined to have failed, whereas, in the intervention group, only 21 catheters (11.1%) failed. There was a significant difference between each group regarding the ratio of catheter failure adjusted according to IPW (p = 0.003). The relative risk reduction of the intervention for catheter failure was 0.60 (95% CI: 0.47–0.71). Care protocols, including assessment of vein diameter, vein depth, and catheter tip location using ultrasound examination for reducing mechanical irritation is a promising method to reduce catheter failure incidence.
Transition between protein-like and polymer-like dynamic behavior: Internal friction in unfolded apomyoglobin depends on denaturing conditions
Authors: Balacescu Livia , Schrader Tobias E. , Radulescu Aurel , Zolnierczuk Piotr , Holderer Olaf , Pasini Stefano , Fitter Jörg , Stadler Andreas M.
Published: January 2020

Equilibrium dynamics of different folding intermediates and denatured states is strongly connected to the exploration of the conformational space on the nanosecond time scale and might have implications in understanding protein folding. For the first time, the same protein system apomyoglobin has been investigated using neutron spin-echo spectroscopy in different states: native-like, partially folded (molten globule) and completely unfolded, following two different unfolding paths: using acid or guanidinium chloride (GdmCl). While the internal dynamics of the native-like state can be understood using normal mode analysis based on high resolution structural information of myoglobin, for the unfolded and even for the molten globule states, models from polymer science are employed. The Zimm model accurately describes the slowly-relaxing, expanded GdmCl-denaturated state, ignoring the individuality of the different aminoacid side chain. The dynamics of the acid unfolded and molten globule state are similar in the framework of the Zimm model with internal friction, where the chains still interact and hinder each other: the first Zimm relaxation time is as large as the internal friction time. Transient formation of secondary structure elements in the acid unfolded and presence ofα-helices in the molten globule state lead to internal friction to a similar extent.
Nuclear bodies formed by polyQ-ataxin-1 protein are liquid RNA/protein droplets with tunable dynamics
Authors: Zhang Sunyuan , Hinde Elizabeth , Parkyn Schneider Molly , Jans David A. , Bogoyevitch Marie A.
Published: January 2020

A mutant form of the ataxin-1 protein with an expanded polyglutamine (polyQ) tract is the underlying cause of the inherited neurodegenerative disease spinocerebellar ataxia 1 (SCA1). In probing the biophysical features of the nuclear bodies (NBs) formed by polyQ-ataxin-1, we defined ataxin-1 NBs as spherical liquid protein/RNA droplets capable of rapid fusion. We observed dynamic exchange of the ataxin-1 protein into these NBs; notably, cell exposure to a pro-oxidant stress could trigger a transition to slower ataxin-1 exchange, typical of a hydrogel state, which no longer showed the same dependence on RNA or sensitivity to 1,6-hexanediol. Furthermore, we could alter ataxin-1 exchange dynamics either through modulating intracellular ATP levels, RNA helicase inhibition, or siRNA-mediated depletion of select RNA helicases. Collectively, these findings reveal the tunable dynamics of the liquid RNA/protein droplets formed by polyQ-ataxin-1.
General surface circulation controls the interannual fluctuations of anchovy stock biomass in the Central Mediterranean Sea
Authors: Patti Bernardo , Torri Marco , Cuttitta Angela
Published: January 2020

The sustainable exploitation of small pelagic fish populations, characterized by short life span and early age at first reproduction, is typically more influenced by the success of annual recruitment rather than by fishing mortality. Recruitment strength, in turn, is related to the high environmental variability characterizing the pelagic fish habitats, able to strongly affect the survival of early stages, from hatching to recruitment. Here, we consider the case study of anchovy (Engraulis encrasicolus) stock in the Strait of Sicily (Central Mediterranean). The interannual fluctuations exhibited over an 18-year long period by this fish population was found to be mainly linked to surface circulation patterns, as far as they are able to control retention/dispersal processes of larval stages. We firstly used Lagrangian simulations to reproduce the fate of anchovy early stages during their planktonic phase. Larval retention indices constructed from the output of the simulations were able alone to explain a large proportion of variance (up to 70%) in yearly biomass of the anchovy population, outclassing the other environmental factors considered in this study. Such results are relevant for fisheries management, for all fish stocks characterized by potentially high vulnerability of early life stages.
Evaluation of the effect of GM-CSF blocking on the phenotype and function of human monocytes
Authors: Lotfi Noushin , Zhang Guang-Xian , Esmaeil Nafiseh , Rostami Abdolmohamad
Published: January 2020

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent cytokine that prompts the proliferation of bone marrow-derived macrophages and granulocytes. In addition to its effects as a growth factor, GM-CSF plays an important role in chronic inflammatory autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Reports have identified monocytes as the primary target of GM-CSF; however, its effect on monocyte activation has been under-estimated. Here, using flow cytometry and ELISA we show that GM-CSF induces an inflammatory profile in human monocytes, which includes an upregulated expression of HLA-DR and CD86 molecules and increased production of TNF-α and IL-1β. Conversely, blockage of endogenous GM-CSF with antibody treatment not only inhibited the inflammatory profile of these cells, but also induced an immunomodulatory one, as shown by increased IL-10 production by monocytes. Further analysis with qPCR, flow cytometry and ELISA experiments revealed that GM-CSF blockage in monocytes stimulated production of the chemokine CXCL-11, which suppressed T cell proliferation. Blockade of CXCL-11 abrogated anti-GM-CSF treatment and induced inflammatory monocytes. Our findings show that anti-GM-CSF treatment induces modulatory monocytes that act in a CXCL-11-dependent manner, a mechanism that can be used in the development of novel approaches to treat chronic inflammatory autoimmune diseases.
Using a Taguchi DOE to investigate factors and interactions affecting germination in Miscanthus sinensis
Authors: Awty-Carroll Danny , Ravella Sreenivas , Clifton-Brown John , Robson Paul
Published: January 2020

The Miscanthus genus of perennial grasses is grown for bioenergy and biorenewable feedstocks. Most Miscanthus crop is M × giganteus which is rhizome propagated and therefore difficult to multiply at large scale. Seed-based propagation of new hybrids is being developed, but Miscanthus is difficult to establish from seed especially in the field. Miscanthus is often grown on marginal land adding to the challenge of successfully establishing the crop. Improved understanding of the limits and biology of germination in Miscanthus species is needed. Seed germination is affected by physical and chemical factors that impact germination differently depending on level of exposure. In this investigation of Miscanthus germination, four hormones plus water stress were investigated and the range over which these factors affect germination was determined. An efficient Taguchi experimental design was used to assess the five factors in combination with the effects of light and seed priming. This determined an example of a set of optimum conditions for Miscanthus germination and demonstrated how this could change based on fixing one condition. The experiment showed how environmental stress impacted germination and how treatments such as gibberellic acid could be used to mitigate stress.
Diagnostic Uncertainty and the Epidemiology of Feline Foamy Virus in Pumas (Puma concolor)
Authors: Dannemiller Nicholas G. , Kechejian Sarah , Kraberger Simona , Logan Kenneth , Alldredge Mathew , Crooks Kevin R. , VandeWoude Sue , Carver Scott
Published: January 2020

Feline foamy virus (FFV) is a contact-dependent retrovirus forming chronic, largely apathogenic, infections in domestic and wild felid populations worldwide. Given there is no current ‘gold standard’ diagnostic test for FFV, efforts to elucidate the ecology and epidemiology of the virus may be complicated by unknown sensitivity and specificity of diagnostic tests. Using Bayesian Latent Class Analysis, we estimated the sensitivity and specificity of the only two FFV diagnostic tests available—ELISA and qPCR—as well as the prevalence of FFV in a large cohort of pumas from Colorado. We evaluated the diagnostic agreement of ELISA and qPCR, and whether differences in their diagnostic accuracy impacted risk factor analyses for FFV infection. Our results suggest ELISA and qPCR did not have strong diagnostic agreement, despite FFV causing a persistent infection. While both tests had similar sensitivity, ELISA had higher specificity. ELISA, but not qPCR, identified age to be a significant risk factor, whereas neither qPCR nor ELISA identified sex to be a risk factor. This suggests FFV transmission in pumas may primarily be via non-antagonistic, social interactions between adult conspecifics. Our study highlights that combined use of qPCR and ELISA for FFV may enhance estimates of the true prevalence of FFV and epidemiological inferences.
Overexpression of native IF1 downregulates glucose-stimulated insulin secretion by pancreatic INS-1E cells
Authors: Kahancová Anežka , Sklenář Filip , Ježek Petr , Dlasková Andrea
Published: January 2020

We have previously reported that transient knock-down of ATPase inhibitory factor 1 (IF1) by siRNA upregulates ATP levels and subsequently augments insulin secretion in model pancreatic β-cells INS-1E. Here we investigated how long-term IF1-overexpression impacts pancreatic β-cell bioenergetics and insulin secretion. We generated INS-1E cell line stably overexpressing native IF1. We revealed that IF1 overexpression leads to a substantial decrease in ATP levels and reduced glucose-stimulated insulin secretion. A decrease in total cellular ATP content was also reflected in decreased free ATP cytosolic and mitochondrial levels, as monitored with ATeam biosensor. Consistently, cellular respiration of IF1-overexpressing cells was decreased. 3D structured illumination microscopy (SIM) revealed a higher amount of insulin granules with higher volume in IF1-overexpressing cells. Similar effects occurred when cells were incubated at low glucose concentrations. Noteworthy, activation of PKA by dibutyryl cAMP entirely abolished the inhibitory effect of IF1 overexpression on ATP production and insulin secretion. Mitochondrial network morphology and cristae ultrastructure in INS-1E overexpressing IF1 remained mostly unchanged. Finally, we show that INS-1E cells decrease their IF1 protein levels relative to ATP synthase α-subunit in response to increased glucose. In conclusion, IF1 actively downregulates INS-1E cellular metabolism and reduces their ability to secrete insulin.
Adverse pregnancy outcomes on the risk of overweight offspring: a population-based retrospective study in Xiamen, China
Authors: Chen Yin-ling , Han Li-li , Shi Xiu-lin , Su Wei-juan , Liu Wei , Wang Li-ying , Huang Pei-ying , Lin Ming-zhu , Song Hai-qu , Li Xue-jun
Published: January 2020

The growth trajectory of Chinese preschoolers still remains unclear. Our objective was to determine whether there was an association between adverse pregnancy outcomes and overweight offspring. We analyzed population-based retrospective cohort data from the Medical Birth Registry of Xiamen, which comprised 33,157 children examined from 1 to 6 years of age. Longitudinal analyses were used to evaluate the growth trajectories of offspring body mass index (BMI). Multivariate logistic regression was used to assess the effects of two adverse pregnancy outcomes, gestational diabetes mellitus (GDM) and being large-for-gestational age (LGA), on childhood overweight. Offspring of mothers with GDM and LGA has a higher annual BMI z-score from 1 to 6 years of age (all P < 0.05). But, a higher annual BMI z-score was only observed in children aged 1–5 years in models 1–3. Overall BMI z-score of offspring aged 1–6 who were born to mothers with GDM and LGA were also higher in models 1–3 (all P < 0.05). Additionally, offspring of mothers with GDM and LGA had a higher risk for overweight in model 1, from 1 to 6 years of age (odds ratio (OR), 1.814; 95% confidence interval (CI), 1.657–1.985; P < 0.0001). However, this association was attenuated after adjusting for maternal pre-pregnancy BMI (OR, 1.270; 95% CI, 0.961–1.679; P = 0.0930). Offspring of mothers with GDM and LGA had a higher BMI z-score and increased risk for overweight. Indeed, intrauterine exposure to maternal GDM and LGA could bias offspring to overweight, whereas maternal pre-pregnancy BMI may play a key role in offspring overweight for children born to mothers with GDM and LGA.
Publisher Correction: Prioritizing target-disease associations with novel safety and efficacy scoring methods
Authors: Failli Mario , Paananen Jussi , Fortino Vittorio
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Synergistic effect of cisplatin chemotherapy combined with fractionated radiotherapy regimen in HPV-positive and HPV-negative experimental pharyngeal squamous cell carcinoma
Authors: Kranjc Brezar Simona , Prevc Ajda , Niksic Zakelj Martina , Brozic Andreja , Cemazar Maja , Strojan Primoz , Sersa Gregor
Published: January 2020

HPV infection renders oropharyngeal squamous cell carcinomas more radiosensitive, which results in a favorable prognosis for HPV-positive patients treated with radiation alone or with concurrent platinum-based chemotherapy. The degree of radiosensitivity in fractionated regimens has not yet been fully explored; therefore, in this study, the radiosensitivity of HPV-negative tumors (FaDu) was compared to that of HPV-positive tumors (2A3) subjected to concurrent cisplatin chemotherapy and fractionated versus isoeffective single-dose tumor irradiation in immunodeficient mice. HPV-positive tumors were approximately 5 times more radiosensitive than HPV-negative tumors, irrespective of the irradiation regimen. In both tumor models, concurrent cisplatin chemotherapy and the fractionated regimen induced significant tumor radiosensitization, with a 3- to 4-fold increase in the tumor growth delay compared to that of single-dose irradiation. Furthermore, the degree of radiosensitization induced by cisplatin chemotherapy concurrent with the fractionated irradiation regimen was much higher in HPV-positive tumors, where a synergistic antitumor effect was observed. Specifically, after combined therapy, a 26% higher survival rate was observed in mice with HPV-positive tumors than in mice with HPV-negative tumors. These data suggest that HPV-positive tumors are more radiosensitive to fractionated regimen than to single-dose irradiation with concurrent cisplatin chemotherapy acting synergistically to irradiation.