bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation of the effects of hydrochar application rate on soil amelioration and plant growth in three diverse soils
Authors: de Jager Megan , Giani Luise
Published: April 2021

The hydrothermal carbonization (HTC) of biogas digestate alters the raw materials inherent characteristics to produce a carbon (C)-rich hydrochar (HC), with an improved suitability for soil amelioration. Numerous studies report conflicting impacts of various HC application rates on soil properties and plant growth. In this study, the influence of HC application rate on soil improvement and plant growth aspects was investigated in three diverse soils (Chernozem, Podzol, and Gleysol). Pot trials were conducted in which all soils were amended with 5, 10, 20 and 30% (w/w) HC in quintuplicate, with two controls of pure soil (with and without plants, respectively) also included. Prior to potting, soil samples were collected from all HC-amended soils and controls and analyzed for soil pH, plant available nutrients (PO4-P and K), and microbial activity using standard laboratory and statistical methods. Immediately after potting, a 6-week seed germination experiment using Chinese cabbage was conducted to determine germination success, followed by a plant growth experiment of equal duration and plant species to determine biomass success. At the end of the study (after a total plant growth period of 12 weeks), each pot was sampled and comparatively analyzed for the same soil properties as at the beginning of the study. Soil pH shifted toward the pH of the HC (6.6) in all soils over the course of the study, but was most expressed in the 20% and 30% application rates, confirming the well-documented liming effect of HC. The addition of HC increased the PO4-P and K contents, particularly with 20% and 30% HC amendments. These results are proposedly due to the large labile C fraction of the HC, which is easily degradable by microorganisms. The rapid decomposition of this C fraction prompted the quick release of the HCs inherently high PO4-P and K content into the soil, and in turn, further stimulated microbial activity, until this fraction was essentially depleted. HC addition did not inhibit seed germination at any rate, presumably due to a lack of phytotoxic compounds in the HC from aging and microbial processes, and furthermore, showed no significant impact (positive or negative) on plant growth in any soil, despite improved soil conditions. In conclusion, although less pronounced, soil improvements were still achievable and maintainable at lower application rates (5% and 10%), whereas higher rates did not ensure greater benefits for plant growth. While the addition of high rates of HC did not detrimentally effect soil quality or plant growth, it could lead to leaching if the nutrient supply exceeds plant requirements and the soil’s nutrient retention capacity. Therefore, this study validates the previous study in the effectiveness of the biogas digestate HC for soil amelioration and suggests that smaller regularly repeated HC applications may be recommendable for soil improvement.
The predictive capacity of the high resolution weather research and forecasting model: a year-long verification over Italy
Authors: Apicella L. , Puca S. , Lagasio M. , Meroni A. N. , Milelli M. , Vela N. , Garbero V. , Ferraris L. , Parodi A.
Published: April 2021

Numerical models are operationally used for weather forecasting activities to reduce the risks of several hydro-meteorological disasters. The overarching goal of this work is to evaluate the Weather Research and Forecasting (WRF) model predictive capabilities over the Italian national territory in the year 2018, in two specific cloud resolving configurations. The validation is carried out with a fuzzy logic approach, by comparing the precipitation predicted by the WRF model, and the precipitation observed by the national network. The fuzzy logic technique, by considering different intensity thresholds, allows to identify the reliable spatial scales of the forecasts. The same approach is applied to evaluate the performances of COSMO-2I model, a state-of-the-art numerical model configuration used for operational activities. For the entire year, except for summer, the model predictive capabilities are high, with useful forecasts for structures of medium intensities down toO(10 km) length scales. In summer the skills decrease mainly because of localization errors. The work aims to provide a robust evaluation of the forecast performances of another convection permitting operational meteorological models currently available in Italy.
Mathematical analysis of laboratory microbial experiments demonstrating deterministic chaotic dynamics
Authors: Molz Fred , Faybishenko Boris
Published: April 2021

Presented is a system of four ordinary differential equations and a mathematical analysis of microbiological experiments in a four-component chemostat—nutrient n, rods r, cocci c, and predators p. The analysis is consistent with the conclusion that previous experiments produced features of deterministic chaotic and classical dynamics depending on dilution rate. The surrogate model incorporates as much experimental detail as possible, but necessarily contains unmeasured parameters. The objective is to understand better the differences between model simulations and experimental results in complex microbial populations. The key methodology for simulation of chaotic dynamics, consistent with the measured dilution rate and microbial volume averages, was to cause the preference of p for r vs. c to vary with the r and c concentrations, to make r more competitive for nutrient than c, and to recycle some dying p biomass, leading to a modified version of the Monod kinetics model. Our mathematical model demonstrated that the occurrence of chaotic dynamics requires a predator, p, preference for r versus c to increase significantly with increases in r and c populations. Also included is a discussion of several generalizations of the existing model and a possible involvement of the minimum energy dissipation principle. This principle appears fundamental to thermodynamic systems including living systems. Several new experiments are suggested.
Cultural dimensions in online purchase behavior: Evidence from a cross-cultural study
Authors: Pratesi Francesca , Hu Lala , Rialti Riccardo , Zollo Lamberto , Faraoni Monica
Published: April 2021

The objective of this research is to investigate how cultural differences affect consumers’ online purchase behavior. We reviewed the recent literature on cross-cultural studies on online behavior and building on Hofstede’s theory of cultural dimensions and the theory of planned behavior (TPB), we developed a conceptual model exploring how the dimensions of national culture influence perceptions of website usability, trust, and perceived risk, which in turn impact on intention to use and online purchase behavior. A web-based questionnaire was distributed to a sample of 350 European and Asian consumers actively using Alibaba e-commerce platforms. The conceptual model was validated through a confirmatory factor analysis (CFA), while structural equation modelling (SEM) was used to empirically test the hypothesized relationships among variables. Results showed how culture significantly influenced website usability and perceived risk in European consumers and, in turn, their intention and behavior. Differently, culture significantly influenced trust of Asian consumers, as well as their intention and online behavior. With this study, we contribute to the literature on consumer online purchase behavior from a cross-cultural perspective. As culture emerged among the significant antecedents of mechanisms explaining online purchase behavior, e-tailers should tailor digital marketing strategies according to consumer cultural differences.
Profit optimization for multi-mode repetitive construction project with cash flows using metaheuristics
Authors: Sroka Bartłomiej , Rosłon Jerzy , Podolski Michał , Bożejko Wojciech , Burduk Anna , Wodecki Mieczysław
Published: April 2021

The article presents the profit optimization model for multi-unit construction projects. Such projects constitute a special case of repetitive projects and are common in residential, commercial, and industrial construction projects. Due to the specific character of construction works, schedules of such projects should take into account many different aspects, including durations and costs of construction works, the possibility of selecting alternative execution modes, and specific restrictions (e.g., deadlines for the completion of units imposed by the investor). To solve the NP-hard problem of choosing the order of units’ construction and the best variants of works, the authors used metaheuristic algorithms (simulated annealing and genetic search). The objective function in the presented optimization model was the total profit of the contractor determined on the basis of the mathematical programming model. This model takes into account monthly cash flows subject to direct and indirect costs, penalties for missing deadlines, costs of work group discontinuities, and borrowing losses. The presented problem is very important for maintaining a good financial condition of the enterprise carrying out construction projects. In the article, an experimental analysis of the proposed method of solving the optimization task was carried out in a model that showed high efficiency in obtaining suboptimal solutions. In addition, the operation of the proposed model has been presented on a calculation example. The results obtained in it are fully satisfying.
NX Filtration's hollow-fibre NF technology makes peat water from Indonesia's Mesjid River safe to drink
Authors: Atkinson Simon
Published: April 2021

As reported previously (Membrane Technology , January 2021, page 2), technology from Dutch firm NX Filtration BV, which develops membrane products for treating water, is being used to optimise the Dumai City Water Treatment Plant in Sumatra, Indonesia. The Indonesian company selected to carry out the work – PT. Bayu Surya BaktiKonstruksi, which specialises in the construction of water and wastewater treatment plants – will employ NX Filtration's hollow-fibre nanofiltration (NF) technology to turn, in a single step, the peat water from the local Mesjid River into a valuable source of drinking water, as this follow-up article explains.
Laser and Fiber Optic Gas Absorption Spectroscopy
Authors: Stewart George
Published: April 2021

An invaluable text for the teaching, design, and development of gas sensor technology. This excellent resource synthesizes the fundamental principles of spectroscopy, laser physics, and photonics technology and engineering to enable the reader to fully understand the key issues and apply them in the design of optical gas absorption sensors. It provides a straightforward introduction to low-cost and highly versatile near-IR systems, as well as an extensive review of mid-IR systems. Fibre laser systems for spectroscopy are also examined in detail, especially the emerging technique of frequency comb spectroscopy. Featuring many examples of real-world application and performance, as well as MATLAB computer programs for modeling and simulation, this exceptional work is ideal for postgraduate students, researchers, and professional engineers seeking to gain an in-depth understanding of the principles and applications of fibre-optic and laser-based gas sensors.
Analysis of microbial lipids deposited on Mars Global Simulant (MGS-1) by geomatrix-assisted laser desorption/ionization-mass spectrometry
Authors: dos Santos Alef , Rodrigues-Filho Edson , Homem Manoel Gustavo Petrucelli
Published: April 2021

Lipids are among the organic substances that can work as biosignatures, indicating life in an environment. We present an experimental investigation concerning analysis of lipids from a microbial source deposited on the Mars Global Simulant (MGS-1) regolith by geomatrix-assisted laser desorption/ionization-mass spectrometry (GALDI-MS). Our results indicate that lipids from intact microbial cells of a black yeast strain can be detected in these mimetic samples of Martian soil. These lipid molecules are predominantly associated with the occurrence of adducts in the GALDI-MS spectra. The results can be helpful in the planning of future planetary missions.
Improvements in Cloud and Water Vapor Simulations Over the Tropical Oceans in CMIP6 Compared to CMIP5
Authors: Jiang Jonathan H. , Su Hui , Wu Longtao , Zhai Chengxing , Schiro Kathleen A.
Published: April 2021

Clouds and water vapor are among the most difficult quantities for global climate models to simulate because they are affected by physical processes that operate over scales unresolved by current climate models. We use NASA satellite data to assess the representation of clouds and water vapor structures in 28 climate models that participate in the Coupled Model Intercomparison Project Phase 6 (CMIP6). Each model is assigned numerical scores based on its performance in simulating spatial mean, variance and pattern correlation of multi‐year mean clouds and water vapor structures in lower, middle, upper troposphere, and near the tropopause over tropical oceans. We find measurable improvements in CMIP6 models relative to CMIP5 models for both clouds and water vapor. The differences between models and satellite observations and the spread across the models are reduced. In addition, we find that the models' equilibrium climate sensitivity (ECS) is correlated with overall performance scores for both CMIP5 and CMIP6 models, with a weaker correlation in CMIP6, suggesting that the models that capture better tropical clouds and water vapor distributions tend to have higher ECS. The physical processes responsible for the apparent correlation between ECS and model performance score warrant further study.
Uncovering the Past and Future Climate Drivers of Wheat Yield Shocks in Europe With Machine Learning
Authors: Zhu Peng , Abramoff Rose , Makowski David , Ciais Philippe
Published: April 2021

Recently, yield shocks due to extreme weather events and their consequences for food security have become a major concern. Although long yield time series are available in Europe, few studies have been conducted to analyze them in order to investigate the impact of adverse climate events on yield shocks under current and future climate conditions. Here we designated the lowest 10th percentile of the relative yield anomaly as yield shock and analyzed subnational wheat yield shocks across Europe during the last four decades. We applied a data‐driven attribution framework to quantify primary climate drivers of wheat yield shock probability based on machine learning and game theory, and used this framework to infer the most critical climate variables that will contribute to yield shocks in the future, under two climate change scenarios. During the period 1980–2018, our attribution analysis showed that 32% of the observed wheat yield shocks were primarily driven by water limitation, making it the leading climate driver. Projection to future climate scenarios RCP4.5 and RCP8.5 suggested an increased risk of yield shock and a paradigm shift from water limitation dominated yield shock to extreme warming induced shocks over 2070–2099: 46% and 54% of areas were primarily driven by extreme warming under RCP4.5 and RCP8.5, respectively. A similar analysis conducted on yields simulated by an ensemble of crop models showed that models can capture the negative impact of low water supply but missed the impact of excess water. These discrepancies between observed and simulated yield data call for improvement in crop models.
Dual Carbon Isotope‐Based Source Apportionment and Light Absorption Properties of Water‐Soluble Organic Carbon in PM2.5 Over China
Authors: Mo Yangzhi , Li Jun , Cheng Zhineng , Zhong Guangcai , Zhu Sanyuan , Tian Chongguo , Chen Yingjun , Zhang Gan
Published: April 2021

Water‐soluble organic carbon (WSOC) makes up a large fraction of organic carbon, which has attracted considerable attention due to its light absorption properties and effects on human health. However, the poorly constrained sources and light absorption properties of WSOC give rise to large uncertainties in its effects on climate and health, especially in regions with high pollutant loading. Here, we investigated the sources and light absorption properties of WSOC in 10 cities across China by dual carbon isotope analysis and UV−visible spectrophotometry, respectively. Despite a dominant contribution of nonfossil sources, the fossil source contribution to WSOC was higher in China than in other regions of the world. The average mass absorption efficiency of WSOC at 365 nm (MAE365) the fossil source contribution of WSOC were 1.13 ± 0.37 m2/gC and 39.9 ± 9.4%, respectively; both values were higher in northern than southern China. The nonfossil source contribution and δ13C of WSOC exhibited significant seasonal variations, with higher values in cold seasons, likely in association with enhanced corn residue burning. In addition, higher MAE365 in the cold seasons (fall and winter) was strongly related to enhanced biomass burning emissions. However, the fossil source contribution of WSOC showed a positive relationship with MAE365 in the cold seasons. This may be because the primary fossil WSOC emitted directly by coal combustion and the secondary fossil WSOC generated under the high NOx conditions in the cold seasons would enhance the color of the entire WSOC. To limit the impacts of WSOC on regional climate and human health, it is suggested that mitigation strategies should consider spatiotemporal variation in WSOC sources, its light absorption properties, and the various formation pathways.
A Global High‐Resolution Mesoscale Convective System Database Using Satellite‐Derived Cloud Tops, Surface Precipitation, and Tracking
Authors: Feng Zhe , Leung L. Ruby , Liu Nana , Wang Jingyu , Houze Robert A. , Li Jianfeng , Hardin Joseph C. , Chen Dandan , Guo Jianping
Published: April 2021

A new methodology is developed to construct a global (60°S–60°N) long‐term (2000–2019) high‐resolution (∼10‐km h) mesoscale convective system (MCS) database by tracking MCS jointly using geostationary satellite infrared brightness temperature (Tb) and precipitation feature (PF) characteristics from the Integrated Multi‐satellitE Retrievals for GPM precipitation data sets. Independent validation shows that the satellite‐based MCS data set is able to reproduce important MCS statistics derived from ground‐based radar network observations in the United States and China. We show that by carefully considering key PF characteristics in addition to Tb signatures, the new method significantly improves upon previous Tb‐only methods in detecting MCSs in the midlatitudes for all seasons. Results show that MCSs account for over 50% of annual total rainfall across most of the tropical belt and in selected regions of the midlatitudes, with a strong seasonality over many regions of the globe. The tracking database allows Lagrangian aspects such as MCS lifetime and translational speed and direction to be analyzed. The longest‐lived MCSs preferentially occur over the subtropical oceans. The land MCSs have higher cloud‐tops associated with more intense convection, and oceanic MCSs have much higher rainfall production. While MCSs are observed in many regions of the globe, there are fundamental differences in their dynamic and thermodynamic structures that warrant a better understanding of processes that control their evolution. This global database provides significant opportunities for observational and modeling studies of MCSs, their characteristics, and roles in regional and global water and energy cycles, as well as their hydrologic and other impacts.
Characterization of the Coherence Between Soil Moisture and Precipitation at Regional Scales
Authors: Wu Dongdong , Di Chongli , Wang Tiejun , Wang Lichun , Chen Xi
Published: April 2021

Knowledge of the interplays between soil moisture (SM) and precipitation (P) across different temporal scales is crucial to understand the land‐atmosphere interactions. To examine the factors influencing SM–P coherences, observed long‐term SM and P datasets were obtained from two regional networks (i.e., the Nebraska Mesonet and part of the Soil Climate Analysis Network in Utah) within the continental United States. We evaluated the intricate SM–P interactions by checking high‐ and low‐frequency components using wavelet analysis. The analysis revealed that the global coherence coefficients (GCCs) between SM and P at all frequencies tended to be greater under wetter climatic conditions, suggesting that higher P could promote the SM–P interactions. Moreover, GCCs were more correlated with meteorological factors in Nebraska with wetter climates (e.g., positively with mean annual P and negatively with aridity index at high‐frequency periodicities (daily to 3 monthly), and opposite interactions at low‐frequency periodicities (3 monthly to yearly); whereas, significant correlations emerged between GCCs and soil texture at all frequency periodicities in Utah (e.g., positively with sand fraction while negatively with silt and clay fractions). Part of the reason for the impact of soil texture in Utah was that as the P periodicities weakened with increasing climatic dryness in Utah, soil texture played a more important role in controlling infiltration processes, which directly affected SM–P coherences. Overall, this study demonstrates that SM–P interactions at regional scales were possibly affected by the relative importance of meteorological and local land surface conditions in controlling SM dynamics.
Unsaturated Flow Processes and the Onset of Seasonal Deformation in Slow‐Moving Landslides
Authors: Finnegan N. J. , Perkins J. P. , Nereson A. L. , Handwerger A. L.
Published: April 2021

Predicting rainfall‐induced landslide motion is challenging because shallow groundwater flow is extremely sensitive to the preexisting moisture content in the ground. Here, we use groundwater hydrology theory and numerical modeling combined with five years of field monitoring to illustrate how unsaturated groundwater flow processes modulate the seasonal pore water pressure rise and therefore the onset of motion for slow‐moving landslides. The onset of landslide motion at Oak Ridge earthflow in California’s Diablo Range occurs after an abrupt water table rise to near the landslide surface 52–129 days after seasonal rainfall commences. Model results and theory suggest that this abrupt rise occurs from the advection of a nearly saturated wetting front, which marks the leading edge of the integrated downward flux of seasonal rainfall, to the water table. Prior to this abrupt rise, we observe little measured pore water pressure response within the landslide due to rainfall. However, once the wetting front reaches the water table, we observe nearly instantaneous pore water pressure transmission within the landslide body that is accompanied by landslide acceleration. We cast the timescale to reach a critical pore water pressure threshold using a simple mass balance model that considers variable moisture storage with depth and explains the onset of seasonal landslide motion with a rainfall intensity‐duration threshold. Our model shows that the seasonal response time of slow‐moving landslides is controlled by the dry season vadose zone depth rather than the total landslide thickness.
On the Reliability of Parameter Inferences in a Multiscale Model for Transport in Stream Corridors
Authors: Rathore Saubhagya S. , Jan Ahmad , Coon Ethan T. , Painter Scott L.
Published: April 2021

Nonreacting tracer tests capture information about physical processes in transient storage zones including the hyporheic zone (HZ). However, reliably extracting this information from breakthrough curves (BTCs) and distinguishing the effects of in‐channel dispersion and transient storage are well‐known challenges. Using BTCs from a nonreacting tracer test monitored at multiple locations, we explore ways for reliable parameter estimations. The identifiability of parameters is greatly influenced by the choice of forward and inverse modeling frameworks in addition to the quality of the data. Our forward model is a recently proposed multiscale model that uses subgrid transport models written in the Lagrangian form to represent transport along a diverse set of HZ pathways with a shape‐free distribution of travel times. Joint distributions of HZ and channel parameters are estimated using the Markov Chain Monte Carlo technique. Numerical experiments show ambiguity between channel dispersion and HZ transport when the reach length is too short to allow significant solute‐HZ interaction, the observation period is too brief to observe the tailing behavior, or the solute source is spread in time. In contrast, we obtained reliable parameter estimates by simultaneously fitting BTCs observed at different locations in the test reach using a single set of HZ parameters and section‐specific channel areas and dispersion coefficients. This study demonstrates the estimation of travel time distributions, HZ exchange rates, and channel parameters in a new multiscale approach and offers guidance for extracting reliable parameter estimates from multiple BTCs.
Evolution of Organic Aerosol From Wood Smoke Influenced by Burning Phase and Solar Radiation
Authors: Li Siyuan , Liu Dantong , Hu Dawei , Kong Shaofei , Wu Yangzhou , Ding Shuo , Cheng Yi , Qiu Hao , Zheng Shurui , Yan Qin , Zheng Huang , Hu Kang , Zhang Jiale , Zhao Delong , Liu Quan , Sheng Jiujiang , Ye Jianhuai , He Hui , Ding Deping
Published: April 2021

Emissions of carbonaceous aerosols (black carbon [BC] and organic aerosol [OA]) from biomass burning have important climate and human health impacts. Not only the primary emissions are complicated by combustion phases, but also the evolution after emission is not well understood. In this study, single plumes from residential wood burning, extracted from either flaming or smoldering phase, were injected into our novel chamber, to investigate their evolution in real atmospheric conditions with or without solar radiation. Initial compositions of flaming or smoldering plumes were dominated by BC or OA respectively, with higher NOx emission in flaming. Replicable results showed that in light, smoldering plumes had faster secondary OA (SOA) formation than flaming, due to the higher emissions of volatile organic compounds in smoldering. Furanic and carboxylic acid compounds were found to be the main gaseous precursors and products, respectively. Evaporation and photooxidation concurrently caused increased oxidation in the beginning, but at a later stage of evolution, SOA evolution showed remarkable divergence: enhanced oxidation for smoldering but decreased for flaming plumes, leading to a higher oxygen‐to‐carbon ratio for smoldering than flaming up to 0.25. We found the higher NOx emission in flaming promoted the gaseous fragmentation reactions, while the seeding particles dominated by OA in smoldering may cause these contrasting tendencies of OA oxidation between combustion phases. Distinct particulate/gas emissions and resultant evolutions in producing SOA at different combustion phases should be therefore considered in evaluating the impacts of biomass burning emissions.
Comparison of cardiovascular risk factors between children and adolescents with classes III and IV obesity: findings from the APV cohort
Authors: Reinehr Thomas , Tittel Sascha R. , Holle Rolf , Wiegand Susanna , Gellhaus Ines , Hebebrand Johannes , Greber-Platzer Susanne , Denzer Christian , Linke Sabine , Kiess Wieland , Holl Reinhard W.
Published: April 2021

Objective

Obesity is associated with many cardiovascular risk factors (CVRF) in childhood. There is an ongoing discussion whether there is a linear relationship between degree of overweight and deterioration of CVRFs justifying body mass index (BMI) cut-offs for treatment decisions.

Methods

We studied the impact of BMI-SDS on blood pressure, lipids, and glucose metabolism in 76,660 children (aged 5–25 years) subdivided in five groups: overweight (BMI-SDS 1.3 to <1.8), obesity class I (BMI-SDS 1.8 to <2.3), class II (BMI-SDS 2.3–2.8), class III (BMI-SDS > 2.8–3.3), and class IV (BMI-SDS > 3.3). Analyses were stratified by age and sex.

Results

We found a relationship between BMI-SDS and blood pressure, triglycerides, HDL cholesterol, liver enzymes, and the triglycerides–HDL-cholesterol ratio at any age and sex. Many of these associations lost significance when comparing children with obesity classes III and IV: In females < 14 years and males < 12 years triglycerides and glucose parameters did not differ significantly between classes IV and III obesity. Prevalence of dyslipidemia was significantly higher in class IV compared to class III obesity only in females ≥ 14 years and males ≥ 12 years but not in younger children. In girls < 14 years and in boys of any age, the prevalences of type 2 diabetes mellitus did not differ between classes III and IV obesity.

Conclusions

Since a BMI above the highest BMI cut-off was not associated consistently with dyslipidemia and disturbed glucose metabolism in every age group both in boys and girls, measurements of CVRFs instead of BMI cut-off seem preferable to guide different treatment approaches in obesity such as medications or bariatric surgery.
Vascular normalisation as the stepping stone into tumour microenvironment transformation
Authors: Magnussen Anette L. , Mills Ian G.
Published: April 2021

A functional vascular system is indispensable for drug delivery and fundamental for responsiveness of the tumour microenvironment to such medication. At the same time, the progression of a tumour is defined by the interactions of the cancer cells with their surrounding environment, including neovessels, and the vascular network continues to be the major route for the dissemination of tumour cells in cancer, facilitating metastasis. So how can this apparent conflict be reconciled? Vessel normalisation—in which redundant structures are pruned and the abnormal vasculature is stabilised and remodelled—is generally considered to be beneficial in the course of anti-cancer treatments. A causality between normalised vasculature and improved response to medication and treatment is observed. For this reason, it is important to discern the consequence of vessel normalisation on the tumour microenvironment and to modulate the vasculature advantageously. This article will highlight the challenges of controlled neovascular remodelling and outline how vascular normalisation can shape disease management.
Genetic inactivation of RIP1 kinase activity in rats protects against ischemic brain injury
Authors: Stark Kimberly , Goncharov Tatiana , Varfolomeev Eugene , Xie Luke , Ngu Hai , Peng Ivan , Anderson Keith R. , Verschueren Erik , Choi Meena , Kirkpatrick Donald S. , Easton Amy , Webster Joshua D. , McKenzie Brent S. , Vucic Domagoj , Bingol Baris
Published: April 2021

RIP1 kinase-mediated inflammatory and cell death pathways have been implicated in the pathology of acute and chronic disorders of the nervous system. Here, we describe a novel animal model of RIP1 kinase deficiency, generated by knock-in of the kinase-inactivating RIP1(D138N) mutation in rats. Homozygous RIP1 kinase-dead (KD) rats had normal development, reproduction and did not show any gross phenotypes at baseline. However, cells derived from RIP1 KD rats displayed resistance to necroptotic cell death. In addition, RIP1 KD rats were resistant to TNF-induced systemic shock. We studied the utility of RIP1 KD rats for neurological disorders by testing the efficacy of the genetic inactivation in the transient middle cerebral artery occlusion/reperfusion model of brain injury. RIP1 KD rats were protected in this model in a battery of behavioral, imaging, and histopathological endpoints. In addition, RIP1 KD rats had reduced inflammation and accumulation of neuronal injury biomarkers. Unbiased proteomics in the plasma identified additional changes that were ameliorated by RIP1 genetic inactivation. Together these data highlight the utility of the RIP1 KD rats for target validation and biomarker studies for neurological disorders.
Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma
Authors: Choi Seung Won , Lee Yeri , Shin Kayoung , Koo Harim , Kim Donggeon , Sa Jason K. , Cho Hee Jin , Shin Hye-mi , Lee Se Jeong , Kim Hyunho , Chung Seok , Shin Jihye , Lee Cheolju , Nam Do-Hyun
Published: April 2021

PTEN is one of the most frequently altered tumor suppressor genes in malignant tumors. The dominant-negative effect of PTEN alteration suggests that the aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hotspot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that overexpress these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN. PTEN mutations were categorized into two major subsets: missense mutations in the phosphatase domain and truncal mutations in the C2 domain. We determined the subcellular compartmentalization of four mutant proteins (H93Y, C124S, R130Q, and R173C) from the former group and found that they had distinct localizations; those associated with invasive phenotypes (‘edge mutations’) localized to the cell periphery, while the R173C mutant localized to the nucleus. Invasive phenotypes derived from edge substitutions were unaffected by an anti-PI3K/Akt agent but were disrupted by microtubule inhibitors. PTEN mutations exhibit distinct functional properties regarding their subcellular localization. Further, some missense mutations (‘edge mutations’) in the phosphatase domain caused enhanced invasiveness associated with dysfunctional cytoskeletal assembly, thus suggesting it to be a potent therapeutic target.
Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction
Authors: Xu Jianye , Zhang Jian , Zhang Zongpu , Gao Zijie , Qi Yanhua , Qiu Wei , Pan Ziwen , Guo Qindong , Li Boyan , Zhao Shulin , Guo Xiaofan , Qian Mingyu , Chen Zihang , Wang Shaobo , Gao Xiao , Zhang Shouji , Wang Huizhi , Guo Xing , Zhang Ping , Zhao Rongrong , Xue Hao , Li Gang
Published: April 2021

Exosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.
A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer
Authors: Ye Ying , Dai Qinjin , Qi Hongbo
Published: April 2021

Ovarian cancer (OC) is a highly malignant gynaecological tumour that has a very poor prognosis. Pyroptosis has been demonstrated in recent years to be an inflammatory form of programmed cell death. However, the expression of pyroptosis-related genes in OC and their correlations with prognosis remain unclear. In this study, we identified 31 pyroptosis regulators that were differentially expressed between OC and normal ovarian tissues. Based on these differentially expressed genes (DEGs), all OC cases could be divided into two subtypes. The prognostic value of each pyroptosis-related gene for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 7-gene signature was built and classified all OC patients in the TCGA cohort into a low- or high-risk group. OC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Utilizing the median risk score from the TCGA cohort, OC patients from a Gene Expression Omnibus (GEO) cohort were divided into two risk subgroups, and the low-risk group had increased overall survival (OS) time (P = 0.014). Combined with the clinical characteristics, the risk score was found to be an independent factor for predicting the OS of OC patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched and that the immune status was decreased in the high-risk group. In conclusion, pyroptosis-related genes play important roles in tumour immunity and can be used to predict the prognosis of OCs.
Genetic substructure and complex demographic history of South African Bantu speakers
Authors: Sengupta Dhriti , Choudhury Ananyo , Fortes-Lima Cesar , Aron Shaun , Whitelaw Gavin , Bostoen Koen , Gunnink Hilde , Chousou-Polydouri Natalia , Delius Peter , Tollman Stephen , Gómez-Olivé F. Xavier , Norris Shane , Mashinya Felistas , Alberts Marianne ,   AWI-Gen Study,   H3Africa Consortium, Hazelhurst Scott , Schlebusch Carina M. , Ramsay Michèle
Published: April 2021

South Eastern Bantu-speaking (SEB) groups constitute more than 80% of the population in South Africa. Despite clear linguistic and geographic diversity, the genetic differences between these groups have not been systematically investigated. Based on genome-wide data of over 5000 individuals, representing eight major SEB groups, we provide strong evidence for fine-scale population structure that broadly aligns with geographic distribution and is also congruent with linguistic phylogeny (separation of Nguni, Sotho-Tswana and Tsonga speakers). Although differential Khoe-San admixture plays a key role, the structure persists after Khoe-San ancestry-masking. The timing of admixture, levels of sex-biased gene flow and population size dynamics also highlight differences in the demographic histories of individual groups. The comparisons with five Iron Age farmer genomes further support genetic continuity over ~400 years in certain regions of the country. Simulated trait genome-wide association studies further show that the observed population structure could have major implications for biomedical genomics research in South Africa.
Skilful predictions of the Asian summer monsoon one year ahead
Authors: Takaya Yuhei , Kosaka Yu , Watanabe Masahiro , Maeda Shuhei
Published: April 2021

The interannual variability of the Asian summer monsoon has significant impacts on Asian society. Advances in climate modelling have enabled us to make useful predictions of the seasonal Asian summer monsoon up to approximately half a year ahead, but long-range predictions remain challenging. Here, using a 52-member large ensemble hindcast experiment spanning 1980–2016, we show that a state-of-the-art climate model can predict the Asian summer monsoon and associated summer tropical cyclone activity more than one year ahead. The key to this long-range prediction is successfully simulating El Niño-Southern Oscillation evolution and realistically representing the subsequent atmosphere–ocean response in the Indian Ocean–western North Pacific in the second boreal summer of the prediction. A large ensemble size is also important for achieving a useful prediction skill, with a margin for further improvement by an even larger ensemble.
Integrating science to address food and health within Global Agenda 2030
Authors: McBean Gordon A.
Published: April 2021

When recovering from the pandemic, it is important for Planet Earth to address the Global Agenda 2030, including food and water crises, and to bounce forward sustainably. The World Economic Forum’s Global Risk Report and Global Agenda 2030 provide a framework for action and an integrated global science agenda response, involving food and health, is essential. The UN 2021 Summit on Food Systems provides an opportunity for the global science community to come together to address the Summit’s Action Tracks, including building resilience to vulnerabilities, shocks and stresses. There would be major global benefits to have an international scientific network working with the UN to address the mandates of the UN Food Summit and Global Agenda 2030.
The structure, function and evolution of a complete human chromosome 8
Authors: Logsdon Glennis A. , Vollger Mitchell R. , Hsieh PingHsun , Mao Yafei , Liskovykh Mikhail A. , Koren Sergey , Nurk Sergey , Mercuri Ludovica , Dishuck Philip C. , Rhie Arang , de Lima Leonardo G. , Dvorkina Tatiana , Porubsky David , Harvey William T. , Mikheenko Alla , Bzikadze Andrey V. , Kremitzki Milinn , Graves-Lindsay Tina A. , Jain Chirag , Hoekzema Kendra , Murali Shwetha C. , Munson Katherine M. , Baker Carl , Sorensen Melanie , Lewis Alexandra M. , Surti Urvashi , Gerton Jennifer L. , Larionov Vladimir , Ventura Mario , Miga Karen H. , Phillippy Adam M. , Eichler Evan E.
Published: April 2021

The complete assembly of each human chromosome is essential for understanding human biology and evolution1,2. Here we use complementary long-read sequencing technologies to complete the linear assembly of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.08-Mb centromeric α-satellite array, a 644-kb copy number polymorphism in the β-defensin gene cluster that is important for disease risk, and an 863-kb variable number tandem repeat at chromosome 8q21.2 that can function as a neocentromere. We show that the centromeric α-satellite array is generally methylated except for a 73-kb hypomethylated region of diverse higher-order α-satellites enriched with CENP-A nucleosomes, consistent with the location of the kinetochore. In addition, we confirm the overall organization and methylation pattern of the centromere in a diploid human genome. Using a dual long-read sequencing approach, we complete high-quality draft assemblies of the orthologous centromere from chromosome 8 in chimpanzee, orangutan and macaque to reconstruct its evolutionary history. Comparative and phylogenetic analyses show that the higher-order α-satellite structure evolved in the great ape ancestor with a layered symmetry, in which more ancient higher-order repeats locate peripherally to monomeric α-satellites. We estimate that the mutation rate of centromeric satellite DNA is accelerated by more than 2.2-fold compared to the unique portions of the genome, and this acceleration extends into the flanking sequence.
A biosensor for the direct visualization of auxin
Authors: Herud-Sikimić Ole , Stiel Andre C. , Kolb Martina , Shanmugaratnam Sooruban , Berendzen Kenneth W. , Feldhaus Christian , Höcker Birte , Jürgens Gerd
Published: April 2021

One of the most important regulatory small molecules in plants is indole-3-acetic acid, also known as auxin. Its dynamic redistribution has an essential role in almost every aspect of plant life, ranging from cell shape and division to organogenesis and responses to light and gravity1,2. So far, it has not been possible to directly determine the spatial and temporal distribution of auxin at a cellular resolution. Instead it is inferred from the visualization of irreversible processes that involve the endogenous auxin-response machinery3–7; however, such a system cannot detect transient changes. Here we report a genetically encoded biosensor for the quantitative in vivo visualization of auxin distribution. The sensor is based on the Escherichia coli tryptophan repressor8, the binding pocket of which is engineered to be specific to auxin. Coupling of the auxin-binding moiety with selected fluorescent proteins enables the use of a fluorescence resonance energy transfer signal as a readout. Unlike previous systems, this sensor enables direct monitoring of the rapid uptake and clearance of auxin by individual cells and within cell compartments in planta. By responding to the graded spatial distribution along the root axis and its perturbation by transport inhibitors—as well as the rapid and reversible redistribution of endogenous auxin in response to changes in gravity vectors—our sensor enables real-time monitoring of auxin concentrations at a (sub)cellular resolution and their spatial and temporal changes during the lifespan of a plant.
Sensitive protein alignments at tree-of-life scale using DIAMOND
Authors: Buchfink Benjamin , Reuter Klaus , Drost Hajk-Georg
Published: April 2021

We are at the beginning of a genomic revolution in which all known species are planned to be sequenced. Accessing such data for comparative analyses is crucial in this new age of data-driven biology. Here, we introduce an improved version of DIAMOND that greatly exceeds previous search performances and harnesses supercomputing to perform tree-of-life scale protein alignments in hours, while matching the sensitivity of the gold standard BLASTP.
Differences between children with Down syndrome and typically developing children in adaptive behaviour, executive functions and visual acuity
Authors: de Weger Christine , Boonstra F. Nienke , Goossens Jeroen
Published: April 2021

In children with Down syndrome (DS) development of visual, motor and cognitive functions is atypical. It is unknown whether the visual impairments in children with DS aggravate their lag in cognitive development. Visual impairment and developmental lags in adaptive behaviour and executive functions were assessed in 104 children with DS, 2–16 years, by comparing their adaptive behaviour, executive functions and visual acuity (distant and near) scores against published age-matched norm scores of typically developing children. Associations between these lags were explored. Mean (± SEM) differences to age-matched norms indicated reduced performance in DS: Vineland Screener questionnaire, − 63 ± 3.8 months; task-based Minnesota Executive Function Scale (MEFS), − 46.09 ± 2.07 points; BRIEF-P questionnaire, 25.29 ± 4.66 points; BRIEF parents’ and teachers’ questionnaire, 17.89 ± 3.92 points and 40.10 ± 3.81 points; distant and near visual acuity, 0.51 ± 0.03 LogMAR and 0.63 ± 0.03 LogMAR (near − 0.11 ± 0.04 LogMAR poorer than distant). Adaptive behaviour (Vineland-S) correlated with the severity of visual impairment (r = − 0.396). Children with DS are severely impaired in adaptive behaviour, executive functions and visual acuities (near visual acuity more severely impaired than distant visual acuity). Larger impairment in adaptive behaviour is found in children with larger visual impairment. This supports the idea that visual acuity plays a role in adaptive development.