bluuebunny/crossref_metadata_2025 huggingface dataset:
Bedrock Weathering Controls on Terrestrial Carbon‐Nitrogen‐Climate Interactions
Authors: Dass Pawlok , Houlton Benjamin Z. , Wang Yingping , Wårlind David , Morford Scott
Published: August 2021

Anthropogenic nitrogen deposition is widely considered to increase CO2 sequestration by land plants on a global scale. Here, we demonstrate that bedrock nitrogen weathering contributes significantly more to nitrogen‐carbon interactions than anthropogenic nitrogen deposition. This working hypothesis is based on the introduction of empirical results into a global biogeochemical simulation model over the time period of the mid‐1800s to the end of the 21st century. Our findings suggest that rock nitrogen inputs have contributed roughly 2–11 times more to plant CO2 capture than nitrogen deposition inputs since pre‐industrial times. Climate change projections based on RCP 8.5 show that rock nitrogen inputs and biological nitrogen fixation contribute 2–5 times more to terrestrial carbon uptake than anthropogenic nitrogen deposition though year 2101. Future responses of rock N inputs on plant CO2 capture rates are more signficant at higher latitudes and in mountainous environments, where geological and climate factors promote higher rock weathering rates. The enhancement of plant CO2 uptake via rock nitrogen weathering partially resolves nitrogen‐carbon discrepancies in Earth system models and offers an alternative explanation for lack of progressive nitrogen limitation in the terrestrial biosphere. We conclude that natural N inputs impart major control over terrestrial CO2 sequestration in Earth’s ecosystems.
Biogeochemical and Hydrological Variables Synergistically Influence Nitrate Variability in Coastal Deltaic Wetlands
Authors: Sendrowski Alicia , Castañeda‐Moya Edward , Twilley Robert , Passalacqua Paola
Published: August 2021

Coastal river deltas are centers of surface water nitrate processing, yet the mechanisms controlling spatio‐temporal patterns in nutrient variability are still little understood. Nitrate fluctuations in these systems are controlled by complex interactions between hydrological and biogeochemical drivers, which act together to transport and transform inorganic nutrients. Distinguishing the contributions of these drivers and identifying wetland zones where nitrate processing is occurring can be difficult, yet is critical to make assessments of nutrient removal capacity in deltaic wetlands. To address these issues, we analyze relationships among regional “external” (river discharge, tides, wind) and local “internal” (water level, temperature, turbidity, and nitrate) variables in a deltaic wetland in coastal Louisiana by coupling a process connectivity framework with information theory measures. We classify variable interactions according to whether they work uniquely, redundantly, or synergistically to influence nitrate dynamics and identify timescales of interaction. We find that external drivers work together to influence nitrate transport. Patterns of hydrological and sediment connectivity change over time due to tidal flushing and discharge variation. This connectivity influences the emergence of functional zones where local nitrate fluctuations and temperature and water level process couplings are strong controls on nitrate variability. High vegetation density decreases hydrological process connectivity, even during periods of high river discharge, but it also increases biogeochemical process connections, due to the lengthening of the hydraulic residence time. Based on these results we make recommendations for monitoring nitrate in a wetland.
Genesis of a Severe Dust Storm Over the Indian Subcontinent: Dynamics and Impacts
Authors: Singh Jaydeep , Singh Narendra , Ojha Narendra , Srivastava A. K. , Bisht Deewan Singh , Rajeev Kunjukrishnapillai , Kumar Kiran N. V. P. , Singh Ravi S. , Panwar Vivek , Dhaka S. K. , Kumar Vinay , Nakayama Tomoki , Matsumi Yutaka , Hayashida Sachiko , Dimri A. P.
Published: August 2021

The genesis, dynamics, and impacts of a severe dust storm over the central Himalaya during June 13–17, 2018 have been investigated using in situ measurements, satellite data, and model reanalysis. A low‐pressure system over northern India and prevalence of strong winds (∼20 ms−1) triggered the dust storm leading to poor visibility conditions and five‐fold enhancement in the fine particulate matter (PM2.5) over the central Himalaya. Enhancements in Aerosol Optical Depth (AOD) were observed to be stronger over the Himalayan foothills site (Lumbini) than that over the Indo‐Gangetic Plain (IGP) site‐Gandhi College. The sharp reductions in Angstrom exponent (α) from about 1.2 to 0.3 indicated the dominance of coarse‐mode aerosols during the dust episode. Model results show an enhancement in the dust from 1.5 to 2.5 Tg (∼70%) over the northern Indian subcontinent, with about half of the contribution from the regional source (Thar Desert). Interestingly, dust storm also had significant impacts on turbulent kinetic energy (2.9–9.6 m2 s−2), vertical momentum flux (0.9–3.3 Nm−2), and sensible heat flux (34.8 to −33.9 Wm−2), suggesting turbulent mixing of aerosols and cooling near the surface over the Himalayas. Our study highlights that the large‐scale dust storms exposed to additional dust and pollution from regional sources can profoundly impact the air quality, heat fluxes, and radiative balance over the northern Indian subcontinent. The study would also help in evaluating the results of climate models and to assess the impacts of dust on the hydrological processes and melting Himalayan glaciers.
Asymmetric Brittle Deformation at the Pāpaku Fault, Hikurangi Subduction Margin, NZ, IODP Expedition 375
Authors: Savage Heather M. , Shreedharan Srisharan , Fagereng Åke , Morgan Julia K. , Meneghini Francesca , Wang Maomao , McNamara David D. , Wallace Laura M. , Saffer Demian M. , Barnes Philip M. , Petronotis Katerina E. , LeVay Leah J.
Published: August 2021

Quantifying fault damage zones provides a window into stress distribution and rheology around faults. International Ocean Discovery Program (IODP) Expeditions 372/375 drilled an active thrust splay fault within the Hikurangi subduction margin. The fault, which is hosted in Pleistocene clastic sediments, is surrounded by brittle fractures and faults as well as ductile deformation features. We find that fracture density in the damage zone enveloping the fault is asymmetric, with the hanging wall showing greater overall fracture density and at greater distances from the fault than the footwall. Furthermore, the peak in fracture density occurs within an area of mesoscale folding and localized slip in the hanging wall rather than adjacent to the main fault zone. We attribute the asymmetry in damage to disparate deformation histories between the hanging wall and footwall, greater ductile deformation within the footwall, and/or dynamic stress asymmetry around a propagating rupture. Damage asymmetry is common at shallow depths in subduction zones and influences the mechanical and hydrological properties of the fault, such as channelized fluid flow and fault stability. Finally, we demonstrate that subduction zone faults show similar damage‐displacement scaling as continental faults.
Effect of Lateral and Stress‐Dependent Viscosity Variations on GIA Induced Uplift Rates in the Amundsen Sea Embayment
Authors: Blank B. , Barletta V. , Hu H. , Pappa F. , van der Wal W.
Published: August 2021

Accurate glacial isostatic adjustment (GIA) models are required for correcting measurements of mass change in Antarctica and for improving knowledge of the sub‐surface, especially in areas of large current ice loss such as the Amundsen Sea Embayment (ASE). Regionally, seismic and gravity data suggests lateral differences in viscosity (3D). Furthermore, mantle flow laws allow for a stress‐dependent effective viscosity which changes over time (3D‐s). In this study we investigate whether models with 3D/3D‐s have significant effects on the uplift in the region. We use a finite element model with composite rheology consisting of diffusion and dislocation creep, forced by an ice deglaciation model starting in 1900. We use its uplift predictions as synthetic observations to test the performance of 1D model inversion in the presence of viscosity variations. Stress‐dependent rheology results in lower viscosity beneath the load and a more localized uplift pattern. We demonstrate that the background stress from earlier ice load changes can both increase or decrease the influence of stress‐induced effective viscosity changes. For the ASE, fitting 1D models to 3D model uplift results in a best fitting model with viscosity that represents the average of a large area, while for 3D‐s rheology, local viscosity is more influential. 1D models are statistically indistinguishable from 3D/3D‐s viscosity with current GPS stations. However, 3D and 3D‐s models should be taken into account when accurate uplift and gravity rate patterns are needed, as uplift can differ up to 45% compared to 1D models in between existing GPS stations.
Atmospheric Cold Pools and Their Influence on Sea Surface Temperature in the Bay of Bengal
Authors: Girishkumar M. S. , Joseph Jofia , McPhaden M. J. , Pattabhi Ram Rao E.
Published: August 2021

Recent observations show that atmospheric cold pool (ACP) events are plentiful in the Bay of Bengal (BoB) during summer (May–September) and fall (October–November) and that these events can significantly modify local air‐sea interaction processes on sub‐daily time scales. In this study, we examine whether the magnitude of sea surface temperature (SST) drop associated with ACP events shows any diurnal variability during summer and fall. For this purpose, we use moored buoy data with a 10‐min temporal resolution at 8°, 12°, and 15°N along 90°E and a one‐dimensional mixed layer (ML) model. The analysis shows a reduction in SST (ΔSST) due to ACPs in the BoB during summer and fall, with a maximum magnitude of ΔSST during the afternoon (1200–1600 LST). However, the maximum magnitude of ΔSST during the afternoon is a factor of two higher during fall (∼−0.14°C) than summer (∼−0.07°C). Analysis based on observations and ACP sensitivity experiments indicates that the shallow daytime thermocline and associated thin surface ML is the primary factor regulating the day to night difference in ΔSST associated with ACPs. The presence of this shallow daytime thermocline and thin ML amplifies the effects on SST of net surface heat loss and entrainment of cold sub‐surface water associated with enhanced ACP wind speeds.
Rock Fragments in Shallow Lunar Regolith: Constraints by the Lunar Penetrating Radar Onboard the Chang'E‐4 Mission
Authors: Ding Chunyu , Xiao Zhiyong , Wu Bo , Li Zhaojin , Su Yan , Zhou Bin , Liu Kaijun , Cui Jun
Published: August 2021

It is generally believed that the top centimeters of mature lunar regolith should be dominated by fine particles that contain few rocky fragments, but surface fragments are occasionally visible in mature lunar regolith. Based on amplitudes of surface echoes received by the Lunar Penetrating Radar onboard the Yutu‐2 rover of the Chang'E‐4 mission, we extracted regions with abnormally high relative permittivity that is larger than 4, quantifying the abundance of dense fragments within the top ∼4 cm of the mature regolith along the rover path. We carried out high‐resolution numerical simulations for the propagation of electromagnetic waves, showing that the abnormally high relative permittivity is not caused by local topography but due to the existence of dense materials. Using high‐resolution images obtained by the panorama camera onboard the rover, we performed correlated observation for areas with abnormally high relative permittivity, confirming that some of these dense materials are exposed rocky fragments. However, most of the high relative permittivity areas are not correlated with surface fragments, and some are located beneath floors of highly degraded small impact craters. We found that regolith clumps formed due to impact compaction are not dense enough to cause the abnormally large relative permittivity. Alternatively, the detected dense materials may be melt‐bearing impact breccias in the shallow regolith, which were formed by the host craters. The results revealed a highly heterogeneous structure at shallow depths of mature lunar regolith, revealing a new mechanism of sand‐blasting impacts on the destruction of pores in mature lunar regolith.
Soil Classification: A New Approach for Grouping Soils Using Unsaturated Hydraulic Conductivity Data
Authors: Ghanbarian Behzad , Yokeley Brandon A.
Published: August 2021

Grouping soils based on similarities in their textural, taxonomic, and/or structural properties has broad applications to pedology, hydrology, and soil science. In this study, we present a new approach for classifying soils using hydraulic conductivity data. We apply concepts from critical path analysis and calculate critical pore sizes at various water saturations from the unsaturated hydraulic conductivity curves. Soils with similar critical pore size at the same effective water saturation are then grouped into the same class. To demonstrate the practical application of the proposed soil classification method, we use 102 samples including nine soil textures from the UNSODA database. Applying a curve clustering method, we find eight different soil classes within the studied data set.
Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients
Authors: Cheng Linlin , Zhang Xiaomei , Chen Yu , Wang Dan , Zhang Dong , Yan Songxin , Wang Hongye , Xiao Meng , Liang Te , Li Haolong , Xu Meng , Hou Xin , Dai jiayu , Wu Xian , Li Mingyuan , Lu Minya , Wu Dong , Tian Ran , Zhao Jing , Zhang Yan , Cao Wei , Wang Jinglan , Yan Xiaowei , Zhou Xiang , Liu Zhengyin , Xu Yingchun , He Fuchu , Li Yongzhe , Yu Xiaobo , Zhang Shuyang
Published: August 2021

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host’s innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.
Differential mitochondrial roles for α-synuclein in DRP1-dependent fission and PINK1/Parkin-mediated oxidation
Authors: Krzystek Thomas J. , Banerjee Rupkatha , Thurston Layne , Huang JianQiao , Swinter Kelsey , Rahman Saad Navid , Falzone Tomas L. , Gunawardena Shermali
Published: August 2021

Mitochondria are highly dynamic organelles with strict quality control processes that maintain cellular homeostasis. Within axons, coordinated cycles of fission-fusion mediated by dynamin related GTPase protein (DRP1) and mitofusins (MFN), together with regulated motility of healthy mitochondria anterogradely and damaged/oxidized mitochondria retrogradely, control mitochondrial shape, distribution and size. Disruption of this tight regulation has been linked to aberrant oxidative stress and mitochondrial dysfunction causing mitochondrial disease and neurodegeneration. Although pharmacological induction of Parkinson’s disease (PD) in humans/animals with toxins or in mice overexpressing α-synuclein (α-syn) exhibited mitochondrial dysfunction and oxidative stress, mice lacking α-syn showed resistance to mitochondrial toxins; yet, how α-syn influences mitochondrial dynamics and turnover is unclear. Here, we isolate the mechanistic role of α-syn in mitochondrial homeostasis in vivo in a humanized Drosophila model of Parkinson’s disease (PD). We show that excess α-syn causes fragmented mitochondria, which persists with either truncation of the C-terminus (α-syn1–120) or deletion of the NAC region (α-synΔNAC). Using in vivo oxidation reporters Mito-roGFP2-ORP1/GRX1 and MitoTimer, we found that α-syn-mediated fragments were oxidized/damaged, but α-syn1–120-induced fragments were healthy, suggesting that the C-terminus is required for oxidation. α-syn-mediated oxidized fragments showed biased retrograde motility, but α-syn1–120-mediated healthy fragments did not, demonstrating that the C-terminus likely mediates the retrograde motility of oxidized mitochondria. Depletion/inhibition or excess DRP1-rescued α-syn-mediated fragmentation, oxidation, and the biased retrograde motility, indicating that DRP1-mediated fragmentation is likely upstream of oxidation and motility changes. Further, excess PINK/Parkin, two PD-associated proteins that function to coordinate mitochondrial turnover via induction of selective mitophagy, rescued α-syn-mediated membrane depolarization, oxidation and cell death in a C-terminus-dependent manner, suggesting a functional interaction between α-syn and PINK/Parkin. Taken together, our findings identify distinct roles for α-syn in mitochondrial homeostasis, highlighting a previously unknown pathogenic pathway for the initiation of PD.
A Catalogus Immune Muris of the mouse immune responses to diverse pathogens
Authors: Barlier Céline , Barriales Diego , Samosyuk Alexey , Jung Sascha , Ravichandran Srikanth , Medvedeva Yulia A. , Anguita Juan , del Sol Antonio
Published: August 2021

Immunomodulation strategies are crucial for several biomedical applications. However, the immune system is highly heterogeneous and its functional responses to infections remains elusive. Indeed, the characterization of immune response particularities to different pathogens is needed to identify immunomodulatory candidates. To address this issue, we compiled a comprehensive map of functional immune cell states of mouse in response to 12 pathogens. To create this atlas, we developed a single-cell-based computational method that partitions heterogeneous cell types into functionally distinct states and simultaneously identifies modules of functionally relevant genes characterizing them. We identified 295 functional states using 114 datasets of six immune cell types, creating aCatalogus Immune Muris. As a result, we found common as well as pathogen-specific functional states and experimentally characterized the function of an unknown macrophage cell state that modulates the response toSalmonellaTyphimurium infection. Thus, we expect ourCatalogus Immune Muristo be an important resource for studies aiming at discovering new immunomodulatory candidates.
LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia
Authors: Tang Doudou , Luo Yujiao , Jiang Yafeng , Hu Piao , Peng Hongling , Wu Shangjie , Zhang Guangsen , Wang Yewei
Published: August 2021

Uncontrolled proliferation is the hallmark of cancer cells. Previous studies mainly focused on the role of protein-coding genes in cancer cell proliferation. Emerging evidence showed that long non-coding RNAs (lncRNAs) also play critical roles in cancer cell proliferation and growth. LncRNA KCNQ1OT1 is found to contribute to carcinogenesis, but its role in acute promyelocytic leukemia (APL) is unclear. In this study, by analyzing data from Gene Expression Omnibus, The Cancer Genome Atlas database and our clinical samples, we found that KCNQ1OT1 was selectively highly expressed in APL. Functional assays demonstrated that knockdown of KCNQ1OT1 reduced APL cell proliferation and increased apoptosis. Further evidence showed that KCNQ1OT1 was mainly located in the cytoplasm of APL patient-derived NB4 cells and APL patient bone marrow samples. Mechanistically, KCNQ1OT1 bound to RNA binding protein FUS, and silencing either KCNQ1OT1 or FUS reduced the expression level and stability of MAP3K1 mRNA. Whereas KCNQ1OT1 and FUS did not affect each other. Importantly, knockdown of MAP3K1 impaired APL cell proliferation. Finally, c-Myc transactivated KCNQ1OT1 in APL cells through binding to its promoter while knockdown of c-Myc decreased KCNQ1OT1 expression. Our results not only revealed that c-Myc transactivated KCNQ1OT1 and upregulated KCNQ1OT1 promoted APL cell proliferation, but also demonstrated that KCNQ1OT1 bound to FUS to synergistically stabilize MAP3K1 mRNA, thus facilitating APL cell proliferation. This study established a previously unidentified role of KCNQ1OT1 in the development of APL, and KCNQ1OT1 may serve as a potential therapeutic target for APL.
Systematic profiling of SARS-CoV-2-specific IgG responses elicited by an inactivated virus vaccine identifies peptides and proteins for predicting vaccination efficacy
Authors: Ma Ming-Liang , Shi Da-Wei , Li Yang , Hong Wei , Lai Dan-Yun , Xue Jun-Biao , Jiang He-Wei , Zhang Hai-Nan , Qi Huan , Meng Qing-Feng , Guo Shu-Juan , Xia De-Ju , Hu Jin-Jun , Liu Shuo , Li He-Yang , Zhou Jie , Wang Wei , Yang Xiao , Fan Xiong-Lin , Lei Qing , Chen Wei-Jun , Li Ce-Sheng , Yang Xiao-Ming , Xu Si-Hong , Wei Hong-Ping , Tao Sheng-Ce
Published: August 2021

One of the best ways to control COVID-19 is vaccination. Among the various SARS-CoV-2 vaccines, inactivated virus vaccines have been widely applied in China and many other countries. To understand the underlying protective mechanism of these vaccines, it is necessary to systematically analyze the humoral responses that are triggered. By utilizing a SARS-CoV-2 microarray with 21 proteins and 197 peptides that fully cover the spike protein, antibody response profiles of 59 serum samples collected from 32 volunteers immunized with the inactivated virus vaccine BBIBP-CorV were generated. For this set of samples, the microarray results correlated with the neutralization titers of the authentic virus, and two peptides (S1-5 and S2-22) were identified as potential biomarkers for assessing the effectiveness of vaccination. Moreover, by comparing immunized volunteers to convalescent and hospitalized COVID-19 patients, the N protein, NSP7, and S2-78 were identified as potential biomarkers for differentiating COVID-19 patients from individuals vaccinated with the inactivated SARS-CoV-2 vaccine. The comprehensive profile of humoral responses against the inactivated SARS-CoV-2 vaccine will facilitate a deeper understanding of the vaccine and provide potential biomarkers for inactivated virus vaccine-related applications.
The associations between whole grain and refined grain intakes and serum C-reactive protein
Authors: Taskinen Riikka E. , Hantunen Sari , Tuomainen Tomi-Pekka , Virtanen Jyrki K.
Published: August 2021

Background/objectives

Epidemiological studies suggest that whole grain intake has inverse associations with low-grade inflammation, but findings regarding refined grains are inconclusive. Our objective was to investigate whether consumption of whole or refined grains is associated with serum high sensitivity CRP (hs-CRP).

Subjects/methods

The study included 756 generally healthy men and women aged 53–73 years from the Kuopio Ischaemic Heart Disease Risk Factory Study, examined in 1999–2001. Dietary intakes were assessed using 4-day food records. ANCOVA and linear regression were used for analyses.

Results

The mean intake of whole and refined grains was 136 g/day (SD 80) and 84 g/day (SD 46), respectively. Higher whole grain intake was associated with lower hs-CRP concentration and higher refined grain intake with higher concentration after adjustment for lifestyle and dietary factors. Each 50 g/d higher whole grain intake was associated with 0.12 mg/L (95% Cl 0.02–0.21 mg/L) lower hs-CRP concentration and each 50 g/d higher refined grain intake with 0.23 mg/L (95% Cl 0.08–0.38) higher concentration. Adjustment for fibre from grains attenuated the associations especially with whole grains. There were no statistically significant interactions according to gender or BMI (P for interactions >0.065).

Conclusions

The results of this study suggest that higher intake of whole grains is associated with lower concentrations of hs-CRP and higher intake of refined grains is associated with higher concentrations. However, especially the association with whole grain intake was attenuated after adjusting for fibre intake from grains, suggesting that cereal fibre may partly explain the association.
Intellectual disability and microcephaly associated with a novel CHAMP1 mutation
Authors: Asakura Yuta , Osaka Hitoshi , Aoi Hiromi , Mizuguchi Takeshi , Matsumoto Naomichi , Yamagata Takanori
Published: August 2021

Mutations in a number of genes related to chromosomal segregation reportedly cause developmental disorders, e.g., chromosome alignment-maintaining phosphoprotein 1 (CHAMP1). We report on an 8-year-old Japanese girl who presented with a developmental disorder and microcephaly and carries a novel nonsense mutation in CHAMP1. Therefore, CHAMP1 mutation should be considered as a differential diagnosis of global developmental delay and microcephaly.
A hierarchical approach to removal of unwanted variation for large-scale metabolomics data
Authors: Kim Taiyun , Tang Owen , Vernon Stephen T. , Kott Katharine A. , Koay Yen Chin , Park John , James David E. , Grieve Stuart M. , Speed Terence P. , Yang Pengyi , Figtree Gemma A. , O’Sullivan John F. , Yang Jean Yee Hwa
Published: August 2021

Liquid chromatography-mass spectrometry-based metabolomics studies are increasingly applied to large population cohorts, which run for several weeks or even years in data acquisition. This inevitably introduces unwanted intra- and inter-batch variations over time that can overshadow true biological signals and thus hinder potential biological discoveries. To date, normalisation approaches have struggled to mitigate the variability introduced by technical factors whilst preserving biological variance, especially for protracted acquisitions. Here, we propose a study design framework with an arrangement for embedding biological sample replicates to quantify variance within and between batches and a workflow that uses these replicates to remove unwanted variation in a hierarchical manner (hRUV). We use this design to produce a dataset of more than 1000 human plasma samples run over an extended period of time. We demonstrate significant improvement of hRUV over existing methods in preserving biological signals whilst removing unwanted variation for large scale metabolomics studies. Our tools not only provide a strategy for large scale data normalisation, but also provides guidance on the design strategy for large omics studies.
Blurring the boundary between homogenous and heterogeneous catalysis using palladium nanoclusters with dynamic surfaces
Authors: Cano Israel , Weilhard Andreas , Martin Carmen , Pinto Jose , Lodge Rhys W. , Santos Ana R. , Rance Graham A. , Åhlgren Elina Harriet , Jónsson Erlendur , Yuan Jun , Li Ziyou Y. , Licence Peter , Khlobystov Andrei N. , Alves Fernandes Jesum
Published: August 2021

Using a magnetron sputtering approach that allows size-controlled formation of nanoclusters, we have created palladium nanoclusters that combine the features of both heterogeneous and homogeneous catalysts. Here we report the atomic structures and electronic environments of a series of metal nanoclusters in ionic liquids at different stages of formation, leading to the discovery of Pd nanoclusters with a core of ca. 2 nm surrounded by a diffuse dynamic shell of atoms in [C4C1Im][NTf2]. Comparison of the catalytic activity of Pd nanoclusters in alkene cyclopropanation reveals that the atomically dynamic surface is critically important, increasing the activity by a factor of ca. 2 when compared to compact nanoclusters of similar size. Catalyst poisoning tests using mercury and dibenzo[a,e]cyclooctene show that dynamic Pd nanoclusters maintain their catalytic activity, which demonstrate their combined features of homogeneous and heterogeneous catalysts within the same material. Additionally, kinetic studies of cyclopropanation of alkenes mediated by the dynamic Pd nanoclusters reveal an observed catalyst order of 1, underpinning the pseudo-homogeneous character of the dynamic Pd nanoclusters.
DNA dynamics and computation based on toehold-free strand displacement
Authors: Kang Hong , Lin Tong , Xu Xiaojin , Jia Qing-Shan , Lakerveld Richard , Wei Bryan
Published: August 2021

We present a simple and effective scheme of a dynamic switch for DNA nanostructures. Under such a framework of toehold-free strand displacement, blocking strands at an excess amount are applied to displace the complementation of specific segments of paired duplexes. The functional mechanism of the scheme is illustrated by modelling the base pairing kinetics of competing strands on a target strand. Simulation reveals the unique properties of toehold-free strand displacement in equilibrium control, which can be leveraged for information processing. Based on the controllable dynamics in the binding of preformed DNA nanostructures, a multi-input-multi-output (MIMO) Boolean function is controlled by the presence of the blockers. In conclusion, we implement two MIMO Boolean functions (one with 4-bit input and 2-bit output, and the other with 16-bit input and 8-bit output) to showcase the controllable dynamics.
Access to cationic polyhedral carboranes via dynamic cage surgery with N-heterocyclic carbenes
Authors: Vrána Jan , Holub Josef , Samsonov Maksim A. , Růžičková Zdeňka , Cvačka Josef , McKee Michael L. , Fanfrlík Jindřich , Hnyk Drahomír , Růžička Aleš
Published: August 2021

Polyhedral boranes and heteroboranes appear almost exclusively as neutral or anionic species, while the cationic ones are protonated at exoskeletal heteroatoms or they are instable. Here we report the reactivity of 10-vertex closo-dicarbadecaboranes with one or two equivalents of N-heterocyclic carbene to 10-vertex nido mono- and/or bis-carbene adducts, respectively. These complexes easily undergo a reaction with HCl to give cages of stable and water soluble 10-vertex nido-type cations with protonation in the form of a BHB bridge or 10-vertex closo-type cations containing one carbene ligand when originating from closo-1,10-dicarbadecaborane. The reaction of a 10-vertex nido mono-carbene adduct with phosphorus trichloride gives nido-11-vertex 2-phospha-7,8-dicarbaundecaborane, which undergoes an oxidation of the phosphorus atom to P = O, while the product of a bis-carbene adduct reaction is best described as a distorted C2B6H8 fragment bridged by the (BH)2PCl2+ moiety.
Phylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota
Authors: Galindo Luis Javier , López-García Purificación , Torruella Guifré , Karpov Sergey , Moreira David
Published: August 2021

Compared to multicellular fungi and unicellular yeasts, unicellular fungi with free-living flagellated stages (zoospores) remain poorly known and their phylogenetic position is often unresolved. Recently, rRNA gene phylogenetic analyses of two atypical parasitic fungi with amoeboid zoospores and long kinetosomes, the sanchytrids Amoeboradix gromovi and Sanchytrium tribonematis, showed that they formed a monophyletic group without close affinity with known fungal clades. Here, we sequence single-cell genomes for both species to assess their phylogenetic position and evolution. Phylogenomic analyses using different protein datasets and a comprehensive taxon sampling result in an almost fully-resolved fungal tree, with Chytridiomycota as sister to all other fungi, and sanchytrids forming a well-supported, fast-evolving clade sister to Blastocladiomycota. Comparative genomic analyses across fungi and their allies (Holomycota) reveal an atypically reduced metabolic repertoire for sanchytrids. We infer three main independent flagellum losses from the distribution of over 60 flagellum-specific proteins across Holomycota. Based on sanchytrids’ phylogenetic position and unique traits, we propose the designation of a novel phylum, Sanchytriomycota. In addition, our results indicate that most of the hyphal morphogenesis gene repertoire of multicellular fungi had already evolved in early holomycotan lineages.
The killifish visual system as an in vivo model to study brain aging and rejuvenation
Authors: Vanhunsel Sophie , Bergmans Steven , Beckers An , Etienne Isabelle , Van houcke Jolien , Seuntjens Eve , Arckens Lut , De Groef Lies , Moons Lieve
Published: August 2021

Worldwide, people are getting older, and this prolonged lifespan unfortunately also results in an increased prevalence of age-related neurodegenerative diseases, contributing to a diminished life quality of elderly. Age-associated neuropathies typically include diseases leading to dementia (Alzheimer’s and Parkinson’s disease), as well as eye diseases such as glaucoma and age-related macular degeneration. Despite many research attempts aiming to unravel aging processes and their involvement in neurodegeneration and functional decline, achieving healthy brain aging remains a challenge. The African turquoise killifish (Nothobranchius furzeri) is the shortest-lived reported vertebrate that can be bred in captivity and displays many of the aging hallmarks that have been described for human aging, which makes it a very promising biogerontology model. As vision decline is an important hallmark of aging as well as a manifestation of many neurodegenerative diseases, we performed a comprehensive characterization of this fish’s aging visual system. Our work reveals several aging hallmarks in the killifish retina and brain that eventually result in a diminished visual performance. Moreover, we found evidence for the occurrence of neurodegenerative events in the old killifish retina. Altogether, we introduce the visual system of the fast-aging killifish as a valuable model to understand the cellular and molecular mechanisms underlying aging in the vertebrate central nervous system. These findings put forward the killifish for target validation as well as drug discovery for rejuvenating or neuroprotective therapies ensuring healthy aging.
Degradation of ancient Maya carved tuff stone at Copan and its bacterial bioconservation
Authors: Elert Kerstin , Ruiz-Agudo Encarnación , Jroundi Fadwa , Gonzalez-Muñoz Maria Teresa , Fash Barbara W. , Fash William L. , Valentin Nieves , de Tagle Alberto , Rodriguez-Navarro Carlos
Published: August 2021

Much stone sculptural and architectural heritage is crumbling, especially in intense tropical environments. This is exemplified by significant losses on carvings made of tuff stone at the Classic Maya site of Copan. Here we demonstrate that Copan stone primarily decays due to stress generated by humidity-related clay swelling resulting in spalling and material loss, a damaging process that appears to be facilitated by the microbial bioweathering of the tuff stone minerals (particularly feldspars). Such a weathering process is not prevented by traditional polymer- and alkoxysilane-based consolidants applied in the past. As an alternative to such unsuccessful conservation treatments, we prove the effectiveness of a bioconservation treatment based on the application of a sterile nutritional solution that selectively activates the stone´s indigenous bacteria able to produce CaCO3 biocement. The treatment generates a bond with the original matrix to significantly strengthen areas of loss, while unexpectedly, bacterial exopolymeric substances (EPS) impart hydrophobicity and reduce clay swelling. This environmentally-friendly bioconservation treatment is able to effectively and safely preserve fragile stones in tropical conditions, opening the possibility for its widespread application in the Maya area, and elsewhere.
Learning spin liquids on a honeycomb lattice with artificial neural networks
Authors: Li Chang-Xiao , Yang Sheng , Xu Jing-Bo
Published: August 2021

Machine learning methods provide a new perspective on the study of many-body system in condensed matter physics and there is only limited understanding of their representational properties and limitations in quantum spin liquid systems. In this work, we investigate the ability of the machine learning method based on the restricted Boltzmann machine in capturing physical quantities including the ground-state energy, spin-structure factor, magnetization, quantum coherence, and multipartite entanglement in the two-dimensional ferromagnetic spin liquids on a honeycomb lattice. It is found that the restricted Boltzmann machine can encode the many-body wavefunction quite well by reproducing accurate ground-state energy and structure factor. Further investigation on the behavior of multipartite entanglement indicates that the residual entanglement is richer in the gapless phase than the gapped spin-liquid phase, which suggests that the residual entanglement can characterize the spin-liquid phases. Additionally, we confirm the existence of a gapped non-Abelian topological phase in the spin liquids on a honeycomb lattice with a small magnetic field and determine the corresponding phase boundary by recognizing the rapid change of the local magnetization and residual entanglement.
Effects of irrigation and nitrogen on chlorophyll content, dry matter and nitrogen accumulation in sugar beet (Beta vulgaris L.)
Authors: Wang Ning , Fu Fengzhen , Wang Hongrong , Wang Peng , He Shuping , Shao Hongying , Ni Zhen , Zhang Xingmei
Published: August 2021

A 2-year field experiment was conducted to analyze the growth conditions, physical features, yield, and nitrogen use efficiency (NUE) of sugar-beet under limited irrigation conditions in northeast of China. A cultivar H003 was used as plant materials; six treatments (C1–C6) were included: C1, no nitrogen applied, rain-fed; C2, nitrogen (120.00 kg ha−1), rain-fed; C3, no nitrogen applied, hole irrigation for seeding; C4, nitrogen (120.00 kg ha−1), hole irrigation for seeding; C5, no nitrogen applied, hole irrigation for seeding; and C6, nitrogen (120.00 kg ha−1), hole irrigation for seeding, and irrigation at foliage rapid growth stage. The irrigation supply was only 500 mL/plant once. Results showed C6 showed the highest chlorophyll content, dry matter accumulation, yield, etc. and had the best NUE among all the treatments. In conclusion, under the routine fertilization conditions of northeast of China, the cultivation measure of hole irrigation 500 mL/plant for seeding combined with irrigation 500 mL/plant at foliage rapid growth stage greatly improved sugar-beet yield and NUE.
Cost-effectiveness of adjunctive negative pressure wound therapy in paediatric burn care: evidence from the SONATA in C randomised controlled trial
Authors: Frear Cody C. , Griffin Bronwyn R. , Cuttle Leila , Kimble Roy M. , McPhail Steven M.
Published: August 2021

Negative pressure wound therapy (NPWT) has been shown to improve clinical outcomes for children with burns by accelerating wound re-epithelialisation. Its effects on healthcare costs, however, remain poorly understood. The aim of this study was to evaluate the cost-effectiveness of NPWT from a healthcare provider perspective using evidence from the SONATA in C randomised controlled trial, in which 101 children with small-area burns were allocated to either standard care (silver-impregnated dressings) or standard care in combination with adjunctive NPWT. The primary outcome, time to re-epithelialisation, was assessed through a blinded photographic review. Resource usage and costs were prospectively recorded for each participant for up to 6 months. Incremental cost-effectiveness ratios and dominance probabilities were estimated and uncertainty quantified using bootstrap resampling. Mean costs per participant—including dressings, labour, medication, scar management, and theatre operations—were lower in the NPWT group (AUD $903.69) relative to the control group (AUD $1669.01). There was an 89% probability that NPWT was dominant, yielding both faster re-epithelialisation and lower overall costs. Findings remained robust to sensitivity analyses employing alternative theatre costs and time-to-re-epithelialisation estimates for grafted patients. In conclusion, adjunctive NPWT is likely to be a cost-effective and dominant treatment for small-area paediatric burns (ANZCTR.org.au:ACTRN12618000256279).
Combined genetic and chemical screens indicate protective potential for EGFR inhibition to cardiomyocytes under hypoxia
Authors: Heliste Juho , Jokilammi Anne , Vaparanta Katri , Paatero Ilkka , Elenius Klaus
Published: August 2021

The return of blood flow to ischemic heart after myocardial infarction causes ischemia–reperfusion injury. There is a clinical need for novel therapeutic targets to treat myocardial ischemia–reperfusion injury. Here we screened for targets for the treatment of ischemia–reperfusion injury using a combination of shRNA and drug library analyses in HL-1 mouse cardiomyocytes subjected to hypoxia and reoxygenation. The shRNA library included lentiviral constructs targeting 4625 genes and the drug library 689 chemical compounds approved by the Food and Drug Administration (FDA). Data were analyzed using protein–protein interaction and pathway analyses. EGFR inhibition was identified as a cardioprotective mechanism in both approaches. Inhibition of EGFR kinase activity with gefitinib improved cardiomyocyte viability in vitro. In addition, gefitinib preserved cardiac contractility in zebrafish embryos exposed to hypoxia-reoxygenation in vivo. These findings indicate that the EGFR inhibitor gefitinib is a potential candidate for further studies of repurposing the drug for the treatment of myocardial infarction.
Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study
Authors: Hiraoka Atsushi , Kumada Takashi , Tada Toshifumi , Tani Joji , Kariyama Kazuya , Fukunishi Shinya , Atsukawa Masanori , Hirooka Masashi , Tsuji Kunihiko , Ishikawa Toru , Takaguchi Koichi , Itobayashi Ei , Tajiri Kazuto , Shimada Noritomo , Shibata Hiroshi , Ochi Hironori , Kawata Kazuhito , Yasuda Satoshi , Toyoda Hidenori , Aoki Tomoko , Tanaka Takaaki , Ohama Hideko , Nouso Kazuhiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Arai Taeang , Okubo Tomomi , Imai Michitaka , Koizumi Yohei , Nakamura Shinichiro , Joko Koji , Hiasa Yoichi , Kudo Masatoshi ,   The Real-life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)
Published: August 2021

It was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.
Apple quality identification and classification by image processing based on convolutional neural networks
Authors: Li Yanfei , Feng Xianying , Liu Yandong , Han Xingchang
Published: August 2021

This work researched apple quality identification and classification from real images containing complicated disturbance information (background was similar to the surface of the apples). This paper proposed a novel model based on convolutional neural networks (CNN) which aimed at accurate and fast grading of apple quality. Specific, complex, and useful image characteristics for detection and classification were captured by the proposed model. Compared with existing methods, the proposed model could better learn high-order features of two adjacent layers that were not in the same channel but were very related. The proposed model was trained and validated, with best training and validation accuracy of 99% and 98.98% at 2590th and 3000th step, respectively. The overall accuracy of the proposed model tested using an independent 300 apple dataset was 95.33%. The results showed that the training accuracy, overall test accuracy and training time of the proposed model were better than Google Inception v3 model and traditional imaging process method based on histogram of oriented gradient (HOG), gray level co-occurrence matrix (GLCM) features merging and support vector machine (SVM) classifier. The proposed model has great potential in Apple’s quality detection and classification.
Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease
Authors: Ghosh Nilanjana , Choudhury Priyanka , Joshi Mamata , Bhattacharyya Parthasarathi , Roychowdhury Sushmita , Banerjee Rintu , Chaudhury Koel
Published: August 2021

Asthma—chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease characterised by persistent airflow limitation, which manifests features of both asthma and COPD. These patients have a worse prognosis, in terms of more frequent and severe exacerbations, more frequent symptoms, worse quality of life, increased comorbidities and a faster lung function decline. In absence of clear diagnostic or therapeutic guidelines, ACO presents as a challenge to clinicians. The present study aims to investigate whether ACO patients have a distinct exhaled breath condensate (EBC) metabolic profile in comparison to asthma and COPD. A total of 132 age and BMI matched male smokers were recruited in the exploratory phase which consisted of (i) controls = 33 (ii) asthma = 34 (iii) COPD = 30 and (iv) ACO = 35. Using nuclear magnetic resonance (NMR) metabolomics, 8 metabolites (fatty acid, propionate, isopropanol, lactate, acetone, valine, methanol and formate) were identified to be significantly dysregulated in ACO subjects when compared to both, asthma and COPD. The expression of these dysregulated metabolites were further validated in a fresh patient cohort consisting of (i) asthma = 32 (ii) COPD = 32 and (iii) ACO = 40, which exhibited a similar expression pattern. Multivariate receiver operating characteristic (ROC) curves generated using these metabolites provided a robust ACO classification model. The findings were also integrated with previously identified serum metabolites and inflammatory markers to develop a robust predictive model for differentiation of ACO. Our findings suggest that NMR metabolomics of EBC holds potential as a platform to identify robust, non-invasive biomarkers for differentiating ACO from asthma and COPD.