bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Inversion of Land and Marine Electrical Resistivity Tomography for Submarine Groundwater Discharge and Saltwater Intrusion Characterization
Authors: Hermans T. , Paepen M.
Published: January 2020

Electrical resistivity tomography (ERT) is particularly suited for the characterization of saltwater intrusion and submarine freshwater discharge, given its sensitivity to the electrical conductivity of pore water. A comprehensive survey might combine land ERT collected during low tide and marine ERT acquired with lower sensitivity due to the presence of a seawater layer, most often, inverted separately. In this contribution, we propose a new methodology to jointly invert land and marine ERT acquired along a same profile, bringing them to a common situation at high tide. We first estimate the electrical resistivity distribution under the land profile. Then, we compute a corrected data set for land ERT, simulating a data set collected with the same level of water as the marine ERT. Finally, both land and marine ERT data sets are inverted jointly. We show that the approach allows to better image the freshwater/saltwater distribution across the shoreline.
Atmospheric 81Kr as an Integrator of Cosmic‐Ray Flux on the Hundred‐Thousand‐Year Time Scale
Authors: Zappala J. C. , Baggenstos D. , Gerber C. , Jiang W. , Kennedy B. M. , Lu Z.‐T. , Masarik J. , Mueller P. , Purtschert R. , Visser A.
Published: January 2020

The atmospheric abundance of 81Kr is a global integrator of cosmic rays. It is insensitive to climate shifts, geographical variations, and short‐term solar cycle activity, making it an ideal standard to test models of cosmic‐ray flux on the time scale of 105 years. Here we present the first calculation of absolute 81Kr production rates in the atmosphere, and a measurement of the atmospheric 81Kr/Kr abundance via the Atom Trap Trace Analysis method. The measurement result significantly deviates from previously reported values. The agreement between measurement and model prediction supports the current understanding of the production mechanisms. Additionally, the calculated 81Kr atmospheric inventory over the past 1.5 Myr provides a more accurate input function for radiokrypton dating.
Alfvénic Acceleration Sustains Ganymede's Footprint Tail Aurora
Authors: Szalay J. R. , Allegrini F. , Bagenal F. , Bolton S. J. , Bonfond B. , Clark G. , Connerney J. E. P. , Ebert R. W. , Gershman D. J. , Giles R. S. , Gladstone G. R. , Greathouse T. , Hospodarsky G. B. , Imai M. , Kurth W. S. , Kotsiaros S. , Louarn P. , McComas D. J. , Saur J. , Sulaiman A. H. , Wilson R. J.
Published: January 2020

Integrating simultaneous in situ measurements of magnetic field fluctuations, precipitating electrons, and ultraviolet auroral emissions, we find that Alfvénic acceleration mechanisms are responsible for Ganymede's auroral footprint tail. Magnetic field perturbations exhibit enhanced Alfvénic activity with Poynting fluxes of ~100 mW/m2. These perturbations are capable of accelerating the observed broadband electrons with precipitating fluxes of ~11 mW/m2, such that Alfvénic power is transferred to electron acceleration with ~10% efficiency. The ultraviolet emissions are consistent with in situ electron measurements, indicating 13 ± 3 mW/m2 of precipitating electron flux. Juno crosses flux tubes with both upward and downward currents connected to the auroral tail exhibiting small‐scale structure. We identify an upward electron conic in the downward current region, possibly due to acceleration by inertial Alfvén waves near the Jovian ionosphere. In concert with in situ observations at Io's footprint tail, these results suggest that Alfvénic acceleration processes are broadly applicable to magnetosphere‐satellite interactions.
Does Land Use Age Influence Carbon Cycling in the Tibetan Plateau?
Authors: Justine Meta Francis , Pan Kaiwen , Jean de Dieu Nambajimana , Karamage Fidele , Tadesse Zebene , Pandey Bikram , Yang Wanqin , Wu Fuzhong , Olatunji Olusanya Abio`udun , Nepal Nirdesh , Uchenna Ochege Friday , Tariq Akash , Zhang Lin , Sun Xiaoming
Published: January 2020

Although substantial information had been generated on the effects of land use change on soil organic carbon (SOC) and total nitrogen (TN) storage, studies are absent on multifactorial effects of land use types, land use age, and elevation on SOC and TN storage. SOC and TN were therefore investigated in 30 field sites comprising natural forests, planted forests, shrub, and grasslands. SOC and TN stocks differed and correlated significantly with land use age; the C stocks correlates significantly with land use change compared the TN stocks. However, there was no relation between the C and N stocks with elevation, implying that SOC and TN are solely dependent on land use age. SOC sequestration potentials of the sampled ecosystems were 345.86, 293.19, 266.45, and 251.23 t ha−1 for the natural forests, planted forests, shrub, and grasslands with total mean value of 289.18 t·ha−1 (1,060.42 t·ha−1 CO2−eq). A significant SOC stock loss (17.96%, 29.80%, and 37.66%) occurred in converting natural forests to planted forests, shrub, and grasslands, whereas gains (27.36%, 14.31%, and 5.71%) would occur in reconverting grassland to natural forests, planted forests, and shrublands. Therefore, the C that was lost during deforestation and conversion of natural forests into other land use types could not match the carbon gains thereafter. Our results suggest that land use change and land use age have influenced soil C and N stocks. Moreover, natural forests are better in ecological conservation and restoration of degraded lands. This study provides baseline information for C and N management in ecologically restored and degraded lands.
Quantifying the Feedback Between Rice Architecture, Physiology, and Microclimate Under Current and Future CO2 Conditions
Authors: Sikma M. , Ikawa H. , Heusinkveld B. G. , Yoshimoto M. , Hasegawa T. , Groot Haar L. T. , Anten N. P. R. , Nakamura H. , Vilà‐Guerau de Arellano J. , Sakai H. , Tokida T. , Usui Y. , Evers J. B.
Published: January 2020

To assess the micrometeorological consequences of rice variety choices in relation to rising CO2 associated to climate change, we quantified the interplay between rice architecture, physiology, and microclimate in current (~385 μmol mol−1) and future (~580 μmol mol−1) CO2 microenvironments. Two rice varieties contrasting in canopy structure and physiology were grown embedded in irrigated rice paddies, under elevated CO2 (using a Free‐Air CO2 Enrichment facility) and ambient CO2 conditions. The high‐yielding indica variety Takanari is more photosynthetically active and characterized by a more open canopy than a commonly cultivated variety Koshihikari. Our results show a strong diurnal interplay between solar angle, canopy structure, plant physiology, and the overlying atmosphere. Plant architecture was identified as a strong determinant of the relation between plant physiology and microclimate that in turn affects the surface forcing to the overlying atmosphere. Takanari was able to maintain lower canopy temperature both in current and future CO2 owing to the greater atmospheric mixing and stomatal conductance than Koshihikari. In the perspective of food security, a shift to such a higher‐yielding variety would have consequences on the regional surface energy balance, which subsequently might alter regional weather.
Consensus statement for stability assessment and reporting for perovskite photovoltaics based on ISOS procedures
Authors: Khenkin Mark V. , Katz Eugene A. , Abate Antonio , Bardizza Giorgio , Berry Joseph J. , Brabec Christoph , Brunetti Francesca , Bulović Vladimir , Burlingame Quinn , Di Carlo Aldo , Cheacharoen Rongrong , Cheng Yi-Bing , Colsmann Alexander , Cros Stephane , Domanski Konrad , Dusza Michał , Fell Christopher J. , Forrest Stephen R. , Galagan Yulia , Di Girolamo Diego , Grätzel Michael , Hagfeldt Anders , von Hauff Elizabeth , Hoppe Harald , Kettle Jeff , Köbler Hans , Leite Marina S. , Liu Shengzhong , Loo Yueh-Lin , Luther Joseph M. , Ma Chang-Qi , Madsen Morten , Manceau Matthieu , Matheron Muriel , McGehee Michael , Meitzner Rico , Nazeeruddin Mohammad Khaja , Nogueira Ana Flavia , Odabaşı Çağla , Osherov Anna , Park Nam-Gyu , Reese Matthew O. , De Rossi Francesca , Saliba Michael , Schubert Ulrich S. , Snaith Henry J. , Stranks Samuel D. , Tress Wolfgang , Troshin Pavel A. , Turkovic Vida , Veenstra Sjoerd , Visoly-Fisher Iris , Walsh Aron , Watson Trystan , Xie Haibing , Yıldırım Ramazan , Zakeeruddin Shaik Mohammed , Zhu Kai , Lira-Cantu Monica
Published: January 2020

Improving the long-term stability of perovskite solar cells is critical to the deployment of this technology. Despite the great emphasis laid on stability-related investigations, publications lack consistency in experimental procedures and parameters reported. It is therefore challenging to reproduce and compare results and thereby develop a deep understanding of degradation mechanisms. Here, we report a consensus between researchers in the field on procedures for testing perovskite solar cell stability, which are based on the International Summit on Organic Photovoltaic Stability (ISOS) protocols. We propose additional procedures to account for properties specific to PSCs such as ion redistribution under electric fields, reversible degradation and to distinguish ambient-induced degradation from other stress factors. These protocols are not intended as a replacement of the existing qualification standards, but rather they aim to unify the stability assessment and to understand failure modes. Finally, we identify key procedural information which we suggest reporting in publications to improve reproducibility and enable large data set analysis.
Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories
Authors: Izmailov Sergei A. , Rabdano Sevastyan O. , Hasanbasri Zikri , Podkorytov Ivan S. , Saxena Sunil , Skrynnikov Nikolai R.
Published: January 2020

Site-directed spin labeling (SDSL) ESR is a valuable tool to probe protein systems that are not amenable to characterization by x-ray crystallography, NMR or EM. While general principles that govern the shape of SDSL ESR spectra are known, its precise relationship with protein structure and dynamics is still not fully understood. To address this problem, we designed seven variants of GB1 domain bearing R1 spin label and recorded the corresponding MD trajectories (combined length 180 μs). The MD data were subsequently used to calculate time evolution of the relevant spin density matrix and thus predict the ESR spectra. The simulated spectra proved to be in good agreement with the experiment. Further analysis confirmed that the spectral shape primarily reflects the degree of steric confinement of the R1 tag and, for the well-folded protein such as GB1, offers little information on local backbone dynamics. The rotameric preferences of R1 side chain are determined by the type of the secondary structure at the attachment site. The rotameric jumps involving dihedral angles χ1 and χ2 are sufficiently fast to directly influence the ESR lineshapes. However, the jumps involving multiple dihedral angles tend to occur in (anti)correlated manner, causing smaller-than-expected movements of the R1 proxyl ring. Of interest, ESR spectra of GB1 domain with solvent-exposed spin label can be accurately reproduced by means of Redfield theory. In particular, the asymmetric character of the spectra is attributable to Redfield-type cross-correlations. We envisage that the current MD-based, experimentally validated approach should lead to a more definitive, accurate picture of SDSL ESR experiments.
Sea lice exposure to non-lethal levels of emamectin benzoate after treatments: a potential risk factor for drug resistance
Authors: Lam Chun Ting , Rosanowski Sarah M. , Walker Martin , St-Hilaire Sophie
Published: January 2020

The avermectin derivative emamectin benzoate (EMB) has been widely used by salmon industries around the world to control sea lice infestations. Resistance to this anti-parasitic drug is also commonly reported in these industries. The objective of this study was to quantify the number of sea lice potentially exposed to sub-lethal concentrations of EMB while fish clear the drug after treatments. We assessed juvenile sea lice abundance after 38 EMB treatments on six Atlantic salmon farms, in a small archipelago in British Colombia, Canada, between 2007 and 2018. We fitted a standard EMB pharmacokinetic curve to determine the time when fish treated with this product would have EMB tissue concentrations below the recommended target therapeutic level. During the study, we estimated that for each sea lice treatment there was, on average, an abundance of 0.12 juvenile sea lice per fish during the time period when the concentrations of EMB would have been lower than 60ppb, the recommended therapeutic treatment level for sea lice. The findings from this study on metaphylactic anti-parasitic treatments identify a potential driver for drug resistance in sea lice that should be further explored.
Study of Soil Seed Banks in Ex-closures for Restoration of Degraded Lands in the Central Rift Valley of Ethiopia
Authors: Mohammed Shemsedin Ahmed , Denboba Mekuria Argaw
Published: January 2020

Soil seed banks (SSB) can be important components in the process of rehabilitating degraded lands. Thus, this study was aimed to evaluate the role of SSB to the restoration of degraded lands in six, fifteen and twenty-five year’s ex-closures and adjacent degraded open grazing land (DOGL). Totally, 160 samples of SSB from four soil layers (litter, 0–3 cm, 3–6 cm & 6–9 cm), four sites and ten in a composite of 5 (15 × 15 cm) were collected and tested for seed viability through seed extraction and seedling emergence methods. Species richness and diversity showed a significant difference between the SSB of the ex-closures and DOGL (P = 0.0148 and P = 0.0218 respectively). Seed densities also showed significant differences between the vertical layers of the soils in the ex-closures and DOGL (P = 0.0112) and the interaction effect of the land use type and the vertical soil layers (P = 0.0174). Ex-closures and DOGL scored highest seed densities in their litter and bottom layers of the soils respectively. Most of the woody species in the SSB of older ex-closures were represented in the aboveground flora. Thus, this study has verified that SSB has played a vital role in the restoration of woody species in degraded land through ex-closure practices.
Real-time monitoring of glutathione in living cells using genetically encoded FRET-based ratiometric nanosensor
Authors: Ahmad Mohammad , Anjum Naser A. , Asif Ambreen , Ahmad Altaf
Published: January 2020

Reduced glutathione (GSH) level inside the cell is a critical determinant for cell viability. The level of GSH varies across the cells, tissues and environmental conditions. However, our current understanding of physiological and pathological GSH changes at high spatial and temporal resolution is limited due to non-availability of practicable GSH-detection methods. In order to measure GSH at real-time, a ratiometric genetically encoded nanosensor was developed using fluorescent proteins and fluorescence resonance energy transfer (FRET) approach. The construction of the sensor involved the introduction of GSH binding protein (YliB) as a sensory domain between cyan fluorescent protein (CFP; FRET donor) and yellow fluorescent protein (YFP; FRET acceptor). The developed sensor, named as FLIP-G (Fluorescence Indicator Protein for Glutathione) was able to measure the GSH level under in vitro and in vivo conditions. When the purified FLIP-G was titrated with different concentrations of GSH, the FRET ratio increased with increase in GSH-concentration. The sensor was found to be specific for GSH and also stable to changes in pH. Moreover, in live bacterial cells, the constructed sensor enabled the real-time quantification of cytosolic GSH that is controlled by the oxidative stress level. When expressed in yeast cells, FRET ratio increased with the external supply of GSH to living cells. Therefore, as a valuable tool, the developed FLIP-G can monitor GSH level in living cells and also help in gaining new insights into GSH metabolism.
Epothilone D alters normal growth, viability and microtubule dependent intracellular functions of cortical neurons in vitro
Authors: Clark J. A. , Chuckowree J. A. , Dyer M. S. , Dickson T. C. , Blizzard C. A.
Published: January 2020

Brain penetrant microtubule stabilising agents (MSAs) are being increasingly validated as potential therapeutic strategies for neurodegenerative diseases and traumatic injuries of the nervous system. MSAs are historically used to treat malignancies to great effect. However, this treatment strategy can also cause adverse off-target impacts, such as the generation of debilitating neuropathy and axonal loss. Understanding of the effects that individual MSAs have on neurons of the central nervous system is still incomplete. Previous research has revealed that aberrant microtubule stabilisation can perturb many neuronal functions, such as neuronal polarity, neurite outgrowth, microtubule dependant transport and overall neuronal viability. In the current study, we evaluate the dose dependant impact of epothilone D, a brain penetrant MSA, on both immature and relatively mature mouse cortical neurons in vitro. We show that epothilone D reduces the viability, growth and complexity of immature cortical neurons in a dose dependant manner. Furthermore, in relatively mature cortical neurons, we demonstrate that while cellularly lethal doses of epothilone D cause cellular demise, low sub lethal doses can also affect mitochondrial transport over time. Our results reveal an underappreciated mitochondrial disruption over a wide range of epothilone D doses and reiterate the importance of understanding the dosage, timing and intended outcome of MSAs, with particular emphasis on brain penetrant MSAs being considered to target neurons in disease and trauma.
Efficient whole-cell catalysis for 5-aminovalerate production from L-lysine by using engineered Escherichia coli with ethanol pretreatment
Authors: Cheng Jie , Luo Qing , Duan Huaichuan , Peng Hao , Zhang Yin , Hu Jianping , Lu Yao
Published: January 2020

Microorganisms can utilize biomass to produce valuable chemicals, showing sustainable, renewable and economic advantages compared with traditional chemical synthesis. As a potential five-carbon platform polymer monomer, 5-aminovalerate has been widely used in industrial fields such as clothes and disposable goods. Here we establish an efficient whole-cell catalysis for 5-aminovalerate production with ethanol pretreatment. In this study, the metabolic pathway from L-lysine to 5-aminovalerate was constructed at the cellular level by introducing L-lysine α-oxidase. The newly produced H2O2 and added ethanol both are toxic to the cells, obviously inhibiting their growth. Here, a promising strategy of whole-cell catalysis with ethanol pretreatment is proposed, which greatly improves the yield of 5-aminovalerate. Subsequently, the effects of ethanol pretreatment, substrate concentration, reaction temperature, pH value, metal ion additions and hydrogen peroxide addition on the whole-cell biocatalytic efficiency were investigated. Using 100 g/L of L-lysine hydrochloride as raw material, 50.62 g/L of 5-aminovalerate could be excellently produced via fed-batch bioconversion with the yield of 0.84 mol/mol. The results show that a fast, environmentally friendly and efficient production of 5-aminovalerate was established after introducing the engineered whole-cell biocatalysts. This strategy, combined with ethanol pretreatment, can not only greatly enhance the yield of 5-aminovalerate but also be applied to the biosynthesis of other valuable chemicals.
The plant natural product 2-methoxy-1,4-naphthoquinone stimulates therapeutic neural repair properties of olfactory ensheathing cells
Authors: Chen M. , Vial M. L. , Gee L. , Davis R. A. , St John J. A. , Ekberg J. A. K.
Published: January 2020

Olfactory ensheathing cells (OECs) are crucial for promoting the regeneration of the primary olfactory nervous system that occurs throughout life. Transplantation of OECs has emerged as a promising therapy for nervous system injuries, in particular for spinal cord injury repair. Functional outcomes in both animals and humans are, however, highly variable, primarily because it is difficult to rapidly obtain enough OECs for transplantation. Compounds which can stimulate OEC proliferation without changing the phenotype of the cells are therefore highly sought after. Additionally, compounds which can stimulate favourable cell behaviours such as migration and phagocytic activity are desirable. We conducted a medium-throughput screen testing the Davis open access natural product-based library (472 compounds) and subsequently identified the known plant natural product 2-methoxy-1,4-naphthoquinone as a stimulant of OEC viability. We showed that 2-methoxy-1,4-naphthoquinone: (i) strongly stimulates proliferation over several weeks in culture whilst maintaining the OEC phenotype; (ii) stimulates the phagocytic activity of OECs, and (iii) modulates the cell cycle. We also identified the transcription factor Nrf2 as the compound’s potential molecular target. From these extensive investigations we conclude that 2-methoxy-1,4-naphthoquinone may enhance the therapeutic potential of OECs by stimulating proliferation prior to transplantation.
Astroglial changes in the zona incerta in response to motor cortex stimulation in a rat model of chronic neuropathy
Authors: Cha Myeounghoon , Lee Kyung Hee , Lee Bae Hwan
Published: January 2020

Although astrocytes are known to regulate synaptic transmission and affect new memory formation by influencing long-term potentiation and functional synaptic plasticity, their role in pain modulation is poorly understood. Motor cortex stimulation (MCS) has been used to reduce neuropathic pain through the incertothalamic pathway, including the primary motor cortex (M1) and the zona incerta (ZI). However, there has been no in-depth study of these modulatory effects and region-specific changes in neural plasticity. In this study, we investigated the effects of MCS-induced pain modulation as well as the relationship between the ZI neuroplasticity and MCS-induced pain alleviation in neuropathic pain (NP). MCS-induced threshold changes were evaluated after daily MCS. Then, the morphological changes of glial cells were compared by tissue staining. In order to quantify the neuroplasticity, MAP2, PSD95, and synapsin in the ZI and M1 were measured and analyzed with western blot. In behavioral test, repetitive MCS reduced NP in nerve-injured rats. We also observed recovered GFAP expression in the NP with MCS rats. In the NP with sham MCS rats, increased CD68 level was observed. In the NP with MCS group, increased mGluR1 expression was observed. Analysis of synaptogenesis-related molecules in the M1 and ZI revealed that synaptic changes occured in the M1, and increased astrocytes in the ZI were more closely associated with pain alleviation after MCS. Our findings suggest that MCS may modulate the astrocyte activities in the ZI and synaptic changes in the M1. Our results may provide new insight into the important and numerous roles of astrocytes in the formation and function.
Nearest Neighbour Propensity Score Matching and Bootstrapping for Estimating Binary Patient Response in Oncology: A Monte Carlo Simulation
Authors: Geldof Tine , Popovic Dusan , Van Damme Nancy , Huys Isabelle , Van Dyck Walter
Published: January 2020

Nearest Neighbour (NN) propensity score (PS) matching methods are commonly used in pharmacoepidemiology to estimate treatment response using observational data. Unfortunately, there is limited evidence on the optimal approach for accurately estimating binary treatment response and, more so, to estimate its variance. Bootstrapping, although commonly used to accurately estimate variance, is rarely used together with PS matching. In this Monte Carlo simulation-based study, we examined the performance of bootstrapping used in conjunction with PS matching, as opposed to different NN matching techniques, on a simulated dataset exhibiting varying levels of real world complexity. Thus, an experimental design was set up that independently varied the proportion of patients treated, the proportion of outcomes censored and the amount of PS matches used. Simulation results were externally validated on a real observational dataset obtained from the Belgian Cancer Registry. We found all investigated PS methods to be stable and concordant, with k-NN matching to be optimally dealing with the censoring problem, typically present in chronic cancer-related datasets, whilst being the least computationally expensive. In contrast, bootstrapping used in conjunction with PS matching, being the most computationally expensive, only showed superior results in small patient populations with long-term largely unobserved treatment effects.
Offsetting anthropogenic carbon emissions from biomass waste and mineralised carbon dioxide
Authors: Tripathi Nimisha , Hills Colin D. , Singh Raj S. , Singh Jamuna S.
Published: January 2020

The present work investigates biomass wastes and their ashes for re-use in combination with mineralised CO2 in cement-bound construction products. A range of biomass residues (e.g., wood-derived, nut shells, fibres, and fruit peels) sourced in India, Africa and the UK were ashed and exposed to CO2 gas. These CO2-reactive ashes could mineralise CO2 gas and be used to cement ‘raw’ biomass in solid carbonated monolithic composites. The CO2 sequestered in ashes (125–414 g CO2/kg) and that emitted after incineration (400–500 g CO2/kg) was within the same range (w/w). The CO2-reactive ashes embodied significant amounts of CO2 (147–424 g equivalent CO2/kg ash). Selected ashes were combined with raw biomass and Portland Cement, CEM 1 and exposed to CO2. The use of CEM 1 in the carbonated products was offset by the CO2 mineralised (i.e. samples were ‘carbon negative’, even when 10% w/w CEM 1 was used); furthermore, biomass ashes were a suitable substitute for CEM 1 up to 50% w/w. The approach is conceptually simple, scalable, and can be applicable to a wide range of biomass ashes in a closed ‘emission-capture’ process ‘loop’. An extrapolation of potential for CO2 offset in Europe provides an estimate of CO2 sequestration potential to 2030.
Analyzing changes in the complexity of climate in the last four decades using MERRA-2 radiation data
Authors: Delgado-Bonal Alfonso , Marshak Alexander , Yang Yuekui , Holdaway Daniel
Published: January 2020

The energy balance of the Earth is controlled by the shortwave and longwave radiation emitted to space. Changes in the thermodynamic state of the system over time affect climate and are noticeable when viewing the system as a whole. In this paper, we study the changes in the complexity of climate in the last four decades using data from the Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2). First, we study the complexity of the shortwave and longwave radiation fields independently using Approximate Entropy and Sample Entropy, observing that the rate of complexity change is faster for shortwave radiation. Then, we study the causality of those changes using Transfer Entropy to capture the non-linear dynamics of climate, showing that the changes are mainly driven by the variations in shortwave radiation. The observed behavior of climatic complexity could be explained by the changes in cloud amount, and we research that possibility by investigating its evolution from a complexity perspective using data from the International Satellite Cloud Climatology Project (ISCCP).
Phenotypic and genotypic characterization of families with complex intellectual disability identified pathogenic genetic variations in known and novel disease genes
Authors: Darvish Hossein , Azcona Luis J. , Tafakhori Abbas , Mesias Roxana , Ahmadifard Azadeh , Sanchez Elena , Habibi Arman , Alehabib Elham , Johari Amir Hossein , Emamalizadeh Babak , Jamali Faezeh , Chapi Marjan , Jamshidi Javad , Kajiwara Yuji , Paisán-Ruiz Coro
Published: January 2020

Intellectual disability (ID), which presents itself during childhood, belongs to a group of neurodevelopmental disorders (NDDs) that are clinically widely heterogeneous and highly heritable, often being caused by single gene defects. Indeed, NDDs can be attributed to mutations at over 1000 loci, and all type of mutations, ranging from single nucleotide variations (SNVs) to large, complex copy number variations (CNVs), have been reported in patients with ID and other related NDDs. In this study, we recruited seven different recessive NDD families with comorbidities to perform a detailed clinical characterization and a complete genomic analysis that consisted of a combination of high throughput SNP-based genotyping and whole-genome sequencing (WGS). Different disease-associated loci and pathogenic gene mutations were identified in each family, including known (n = 4) and novel (n = 2) mutations in known genes (NAGLU, SLC5A2, POLR3B, VPS13A, SYN1, SPG11), and the identification of a novel disease gene (n = 1; NSL1). Functional analyses were additionally performed in a gene associated with autism-like symptoms and epileptic seizures for further proof of pathogenicity. Lastly, detailed genotype-phenotype correlations were carried out to assist with the diagnosis of prospective families and to determine genomic variation with clinical relevance. We concluded that the combination of linkage analyses and WGS to search for disease genes still remains a fruitful strategy for complex diseases with a variety of mutated genes and heterogeneous phenotypic manifestations, allowing for the identification of novel mutations, genes, and phenotypes, and leading to improvements in both diagnostic strategies and functional characterization of disease mechanisms.
Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis–associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects
Authors: Kawakubo Mitsuhiro , Tanaka Miyako , Ochi Kozue , Watanabe Akiko , Saka-Tanaka Marie , Kanamori Yohei , Yoshioka Naoki , Yamashita Satoko , Goto Moritaka , Itoh Michiko , Shirakawa Ibuki , Kanai Sayaka , Suzuki Hiromi , Sawada Makoto , Ito Ayaka , Ishigami Masatoshi , Fujishiro Mitsuhiro , Arima Hiroshi , Ogawa Yoshihiro , Suganami Takayoshi
Published: January 2020

Nonalcoholic steatohepatitis (NASH) is a hepatic phenotype of the metabolic syndrome, and increases the risk of cirrhosis and hepatocellular carcinoma (HCC). Although increasing evidence points to the therapeutic implications of certain types of anti-diabetic agents in NASH, it remains to be elucidated whether their effects on NASH are independent of their effects on diabetes. Genetically obese melanocortin 4 receptor–deficient (MC4R-KO) mice fed Western diet are a murine model that sequentially develops hepatic steatosis, NASH, and HCC in the presence of obesity and insulin resistance. In this study, we investigated the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor anagliptin on NASH and HCC development in MC4R-KO mice. Anagliptin treatment effectively prevented inflammation, fibrosis, and carcinogenesis in the liver of MC4R-KO mice. Interestingly, anagliptin only marginally affected body weight, systemic glucose and lipid metabolism, and hepatic steatosis. Histological data and gene expression analysis suggest that anagliptin treatment targets macrophage activation in the liver during the progression from simple steatosis to NASH. As a molecular mechanism underlying anagliptin action, we showed that glucagon-like peptide-1 suppressed proinflammatory and profibrotic phenotypes of macrophages in vitro. This study highlights the glucose metabolism–independent effects of anagliptin on NASH and HCC development.
Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits
Authors: Toch Mathilde , Harris Audrey , Schakman Olivier , Kondratskaya Elena , Boulland Jean-Luc , Dauguet Nicolas , Debrulle Stéphanie , Baudouin Charlotte , Hidalgo-Figueroa Maria , Mu Xiuqian , Gow Alexander , Glover Joel C. , Tissir Fadel , Clotman Frédéric
Published: January 2020

In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut-downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2-null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors.
Two genomic regions encoding exopolysaccharide production systems have complementary functions in B. cereus multicellularity and host interaction
Authors: Caro-Astorga Joaquin , Álvarez-Mena Ana , Hierrezuelo Jesús , Guadix Juan Antonio , Heredia-Ponce Zahira , Arboleda-Estudillo Yohanna , González-Munoz Elena , de Vicente Antonio , Romero Diego
Published: January 2020

Bacterial physiology and adaptation are influenced by the exopolysaccharides (EPS) they produce. These polymers are indispensable for the assembly of the biofilm extracellular matrix in multiple bacterial species. In a previous study, we described the profound gene expression changes leading to biofilm assembly inB. cereusATCC14579 (CECT148). We found that a genomic region putatively dedicated to the synthesis of a capsular polysaccharide (eps2) was overexpressed in a biofilm cell population compared to in a planktonic population, while we detected no change in the transcript abundance from another genomic region (eps1) also likely to be involved in polysaccharide production. Preliminary biofilm assays suggested a mild role for the products of theeps2region in biofilm formation and no function for the products of theeps1region. The aim of this work was to better define the roles of these two regions inB. cereusmulticellularity. We demonstrate that theeps2region is indeed involved in bacterial adhesion to surfaces, cell-to-cell interaction, cellular aggregation and biofilm formation, while theeps1region appears to be involved in a kind of social bacterial motility. Consistent with these results, we further demonstrate using bacterial-host cell interaction experiments that theeps2region is more relevant to the adhesion to human epithelial cells and the zebrafish intestine, suggesting that this region encodes a bacterial factor that may potentiate gut colonization and enhance pathogenicity against humans.
Acoustic waveguide with virtual soft boundary based on metamaterials
Authors: Liu Guang-Sheng , Zhou Yang , Liu Ming-Hao , Yuan Ying , Zou Xin-Ye , Cheng Jian-Chun
Published: January 2020

The use of acoustic metamaterials with novel phenomena to design acoustic waveguides with special properties has obvious potential application value. Here, we propose a virtual soft boundary (VSB) model with high reflectivity and half cycle phase loss, which consists of an acoustic propagation layer and an acoustic metamaterial layer with tube arrays. Then the waveguide designed by the VSB is presented, and the numerical and experimental results show that it can separate acoustic waves at different frequencies without affecting the continuity and the flow of the medium in the space. The VSB waveguide can enrich the functions of acoustic waveguides and provide more application prospects.
Novel human reovirus isolated from children and its long-term circulation with reassortments
Authors: Yamamoto Seiji P. , Motooka Daisuke , Egawa Kazutaka , Kaida Atsushi , Hirai Yuki , Kubo Hideyuki , Motomura Kazushi , Nakamura Shota , Iritani Nobuhiro
Published: January 2020

Mammalian orthoreovirus (MRV), also known as reovirus, was discovered in the 1950s and became the first reported segmented double-stranded RNA virus. MRVs have since been found in a variety of animal species, including humans. However, reports on MRV infections are scarce due to the rarity of their symptomatic occurrence. In Japanese surveillance studies, MRVs have been detected as gastrointestinal pathogens since 1981, with a total of 135 records. In Osaka City, Japan, MRV was first isolated in 1994 from a child with meningitis, and then in 2005 and 2014 from children with gastroenteritis. Here, we conducted the first molecular characterization of human MRV isolates from Japan and identified a novel human reovirus strain belonging to MRV type 2, designated the MRV-2 Osaka strain. This strain, with all three isolates classified, is closely related to MRV-2 isolates from sewage in Taiwan and is relatively close to an MRV-2 isolate from a bat in China. Our data suggest that the MRV-2 Osaka strain, which has circulated amongst humans in Japan for at least two decades, has spread internationally.
Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan
Authors: Zeybek Burak , Manzano Aranzazu , Bianchi Anna , Bonazzoli Elena , Bellone Stefania , Buza Natalia , Hui Pei , Lopez Salvatore , Perrone Emanuele , Manara Paola , Zammataro Luca , Altwerger Gary , Han Chanhee , Tymon-Rosario Joan , Menderes Gulden , Ratner Elena , Silasi Dan-Arin , Huang Gloria S. , Azodi Masoud , Schwartz Peter E. , Santin Alessandro
Published: January 2020

Human trophoblast cell-surface marker (Trop-2) is a surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of human epithelial solid tumors. We investigated the efficacy of sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised of a humanized anti- Trop-2 antibody, conjugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer cell lines and a xenograft model. Trop-2 expression was evaluated in 147 primary cervical tumors by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. For in vitro experiments, two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) cell lines were used. A cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models. Out of 147 primary cervical cancers, 113 were squamous cell carcinomas (SCCs), and 34 were adenocarcinoma/adenosquamous carcinomas. Moderate to strong diffuse staining was seen in 95% (108/113) of SCCs, and 81% (29/34) of adenocarcinoma/adenosquamous cancers on immunohistochemistry. Trop-2 positive cell lines were highly sensitive to sacituzumab govitecan in vitro, with IC50 values in the range of 0.18 to 0.26 nM (p = 0.02, and p = 0.04 for CVX-8, and ADX-3, respectively). In xenografts, a significant tumor growth inhibition was seen after twice-weekly intravenous administration of the drug for three weeks (p < 0.0001, and p = 0.001 for sacituzumab govitecan vs naked antibody, and sacituzumab govitecan vs control-ADC, respectively). Overall survival at 90 days was significantly improved in the sacituzumab govitecan group (p = 0.014). In conclusion, sacituzumab govitecan may represent a novel targeted therapy option in cervical cancer patients overexpressing Trop-2.
Conversion of Broad-Spectrum Antimicrobial Peptides into Species-Specific Antimicrobials Capable of Precisely Targeting Pathogenic Bacteria
Authors: Xu Lin , Shao Changxuan , Li Guoyu , Shan Anshan , Chou Shuli , Wang Jiajun , Ma Qingquan , Dong Na
Published: January 2020

Currently, the majority of antibiotics in clinical use have broad activity spectra, killing pathogenic and beneficial microorganisms indiscriminately. The disruption of the ecological balance of normal flora often results in secondary infections or other antibiotic-associated complications. Therefore, targeted antimicrobial therapies capable of specifically eliminating pathogenic bacteria while retaining the protective benefits of a normal microflora would be advantageous. In this study, we successfully constructed a series of Enterococcus faecalis-targeted antimicrobial peptides from wide-spectrum antimicrobial peptide precursors. These peptides are designed based on fusion of the species-specific peptide pheromone cCF10 and modification of the active region of the antimicrobial peptide. The results showed that cCF10-C4 possessed specific antimicrobial activity against E. faecalis and was not active against other types of bacteria tested. The specificity of this hybrid peptide was shown by the absence of antimicrobial effects in the pheromone-substituted derivative. Further studies indicated that cCF10-C4 and its parent peptide C4 exert their activities by damaging cytoplasmic membrane integrity. The present study reveals the application potential of these molecules as “probiotic” antimicrobials for the control of specific bacterial infections, and it also helps to elucidate the design and construction of species-specific antimicrobials with precise targeting specificity.
Author Correction: A multigene and morphological analysis expands the diversity of the seabod shrimp Xiphopenaeus Smith, 1869 (Decapoda: Penaeidae), with descriptions of two new species
Authors: Carvalho-Batista Abner , Terossi Mariana , Zara Fernando J. , Mantelatto Fernando L. , Costa Rogerio C.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: The light-oxygen effect in biological cells enhanced by highly localized surface plasmon-polaritons
Authors: Khokhlova Anna , Zolotovskii Igor , Sokolovski Sergei , Saenko Yury , Rafailov Edik , Stoliarov Dmitrii , Pogodina Evgenia , Svetukhin Vyacheslav , Sibirny Vladimir , Fotiadi Andrei
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Spin-orbit torques and their associated effective fields from gigahertz to terahertz
Authors: Guimarães Filipe S. M. , Bouaziz Juba , dos Santos Dias Manuel , Lounis Samir
Published: January 2020

Terahertz spintronics offers the prospect of devices which are both faster and more energy-efficient. A promising route to achieve this goal is to exploit current-induced spin-orbit torques. However, the high-frequency properties of these quantities remain unexplored both experimentally and theoretically, within a realistic material-specific approach. Here we investigate the dynamical transverse components of the torques and uncover contributions longitudinal to the magnetic moment capable of changing its magnitude. We show that, while the torques can be drastically altered in the dynamical regime, the effective magnetic fields that accompany them present a frequency-independent behaviour, ranging from the static limit up to the terahertz domain — including the ferromagnetic resonance of the system. The outcomes of this work point to new ways to control magnetic units in next-generation spintronic devices.
A bi-polyoxometallate-based host–guest metal–organic framework
Authors: Wang Sa-Sa , Yang Wen-Bin , Yang Mingxue , Wu Xiao-Yuan , Wu Weiming , Wang Song-Xia , Lin Lang , Lu Can-Zhong
Published: January 2020

An unprecedented bi-POM-based host–guest MOF with ultrahigh stability was synthesized, affording a new absorber for water harvesting from air.
London dispersion-driven hetero-aryl–aryl interactions in 1,2-diaryldisilanes
Authors: Linnemannstöns Marvin , Schwabedissen Jan , Schultz Aaron A. , Neumann Beate , Stammler Hans-Georg , Berger Raphael J. F. , Mitzel Norbert W.
Published: January 2020

1,2-Diaryltetramethyldisilanes X5C6–(SiMe2)2–C6Y5 (X ≠ Y; X, Y = H, F, Cl) adopt counterintuitive dispersion-driven syn-conformations in the crystal and the gas phase, determined by X-ray and electron diffraction.
Comparison study of carbon clusters formation during thermal decomposition of 1,3,5-triamino-2,4,6-trinitrobenzene and benzotrifuroxan: a ReaxFF based sequential molecular dynamics simulation
Authors: Huang Xiaona , Zhao Xuefeng , Long Xinping , Dai Xiaogan , Zhang Kaili , Li Ming , Guo Feng , Qiao Zhiqiang , Wen Yushi
Published: January 2020

The thermal sensitivity difference between TATB and BTF is interpreted from pyrolysis response, initial decomposition mechanism, and clusters formation.
Ionization energies in solution with the QM:QM approach
Authors: Tóth Zsuzsanna , Kubečka Jakub , Muchová Eva , Slavíček Petr
Published: January 2020

Fragment-based QM:QM technique provides an efficient and accurate way for calculating energetics of vertical processes such as ionization.
Revealing stable geometries and magic clusters of hexagonal boron nitride in the nucleation of chemical vapor deposition growth on Ni(111)/Cu(111) surfaces: a theoretical study
Authors: Zhu Hongxia , Zhao Xiaolei , Li Huanhuan , Zhao Ruiqi
Published: January 2020

The stable geometries of both different-sized and magic clusters of CVD-prepared hexagonal BN on Ni(111)/Cu(111) are revealed based on DFT simulations.
A review of mathematical representations of biomolecular data
Authors: Nguyen Duc Duy , Cang Zixuan , Wei Guo-Wei
Published: January 2020

Recently, machine learning (ML) has established itself in various worldwide benchmarking competitions in computational biology, including Critical Assessment of Structure Prediction (CASP) and Drug Design Data Resource (D3R) Grand Challenges.
Kinetic selection of nonradiative excitation in photonic nanoparticles Gd2O3:Er
Authors: Zatsepin Anatoly , Kuznetsova Yulia
Published: January 2020

In Gd2O3:Er nanoparticles, we reveal four parallel channels of Gd3+def → Er3+ energy transfer by kinetic selection of excited states.
Crystal lattice disorder and characteristic features of the low-temperature thermal properties of higher borides
Authors: Novikov V. V. , Matovnikov A. V. , Mitroshenkov N. V. , Shevelkov A. V. , Bud'ko S. L.
Published: January 2020

Heat capacityCP(T) and lattice parametersa(T),b(T) andc(T) of LuB44Si3.5borosilicide are experimentally studied as a function of temperature in the range of 2–300 K.
Correction: Pseudo electron-deficient organometallics: limited reactivity towards electron-donating ligands
Authors: Pitto-Barry Anaïs , Lupan Alexandru , Saidykhan Amie , Zegke Markus , Swift Thomas , Attia Amr A. A. , Lord Rianne M. , Barry Nicolas P. E.
Published: January 2020

Correction for ‘Pseudo electron-deficient organometallics: limited reactivity towards electron-donating ligands’ by Anaïs Pitto-Barry et al., Dalton Trans., 2017, 46, 15676–15683.
Addressing the uncertainty of DFT-determined hydrogenation mechanisms over coinage metal surfaces
Authors: Yang Kunran , Yang Bo
Published: January 2020

Using model reactions and employing a well-trained Bayesian error estimation functional with van der Waals correlation, we estimate the error of DFT calculation results statistically, and therefore predict the reliability of the hydrogenation mechanisms identified.
Discovery and characterization of a novel peptide inhibitor against influenza neuraminidase
Authors: Chen Jianmei , Feng Shujun , Xu Yurui , Huang Xinyu , Zhang Jikang , Chen Jiao , An Xueying , Zhang Yu , Ning Xinghai
Published: January 2020

An optimized octapeptide (errKPAQP), exhibits nanomolar affinity to influenza neuraminidase, can notably inhibit neuraminidase activity, and protect mice from influenza infection in vivo, indicating that errKPAQP is a promising anti-influenza drug.