bluuebunny/crossref_metadata_2025 huggingface dataset:
The Radiality of the Railway Network in Spain during its Early Stages (1830–67): An Assessment of its Territorial Coherence
Authors: Martí-Romero Jaume , San-José Adrià , Martí-Henneberg Jordi
Published: June 2021

The initial period of construction of the Spanish railway network is often criticized for its radial structure, centered on Madrid. In this article, the authors describe the role of the state during the initial stage of railway network construction and confirm that although the political will to construct a centralist network certainly influenced its morphology, other social and economic criteria were also influential. With regard to the political motives behind the radial network, the authors argue that part of this interest could have come in response to perceived needs to strengthen the presence of the Spanish state throughout its national territory and to promote a process of state-building. Finally, it must be stressed that the central hypothesis of our article is that the radial structure of the network was a natural consequence of the strategic geographical position of the country’s capital and of the distribution of economic activity within Spanish territory. The article proposes two methodological approaches for evaluating the extent to which the radial design of the network was justified, bearing in mind the locations of Spain’s most productive regions. The results of these two exercises suggest that the radial configuration with which the Spanish rail network was originally designed probably arose naturally as a result of the distribution of economic activity within the country and of the relative advantage that this bestowed on certain regions due to their geographic position.
Mail, Rail, and Legwork: State and Nation Building through Postal Service in France and Great Britain, 1830–1914
Authors: Schwartz Robert M.
Published: June 2021

A comparative spatial history using GIS, this article examines the similar and differing effects of railway expansion on the growth of postal communications in Great Britain and France from 1830 to the eve of the Great War. It argues that the modern Postal Age in Great Britain and France began in the 1830s. In Britain in 1839, the Parliament obligated private railway companies to convey the Royal Mail throughout the kingdom at reasonable rates. Thereafter, the expansion of postal services and railway networks went hand in hand. Over the years, thousands of new post offices were established and were closer to rail stations than before. As the years wore on the geography of postal communication expanded greatly and by 1914 the majority of rural districts became part of the system of regular, daily mail. In France, a country four or five times larger than England and Wales with a relatively vast rural population, the task of modernizing postal service was a greater challenge. The inauguration of a “rural service” in 1829 employed some 5,000 men as postal carriers to deliver and collect mail throughout the countryside. Thereafter, their numbers grew as new post offices were established to serve villages and small towns with mail deliveries every other day. In the 1880s, under the Third Republic, the state greatly expanded the postal service, deeming it a national mission. It was then that the growing rail network came to shape the national geography of postal service. Hence, at the turn of the century the patterns British and French postal expansions converged.
Stranger, Lover, Friend?
Authors: Böckler Anne , Rennert Annika , Raettig Tim
Published: May 2021

Abstract. Social exclusion, even from minimal game-based interactions, induces negative consequences. We investigated whether the nature of the relationship with the excluder modulates the effects of ostracism. Participants played a virtual ball-tossing game with a stranger and a friend (friend condition) or a stranger and their romantic partner (partner condition) while being fully included, fully excluded, excluded only by the stranger, or excluded only by their close other. Replicating previous findings, full exclusion impaired participants’ basic-need satisfaction and relationship evaluation most severely. While the degree of exclusion mattered, the relationship to the excluder did not: Classic null hypothesis testing and Bayesian statistics showed no modulation of ostracism effects depending on whether participants were excluded by a stranger, a friend, or their partner.
Revisiting Acetonitrile as Tracer of Biomass Burning in Anthropogenic‐Influenced Environments
Authors: Huangfu Yibo , Yuan Bin , Wang Sihang , Wu Caihong , He Xianjun , Qi Jipeng , de Gouw Joost , Warneke Carsten , Gilman Jessica B. , Wisthaler Armin , Karl Thomas , Graus Martin , Jobson Bertram T. , Shao Min
Published: June 2021

Acetonitrile (CH3CN) has been widely employed as biomass burning tracer. However, the current application of CH3CN absolute mixing ratio as the thresholds may misidentify biomass burning due to the interference from other CH3CN sources in anthropogenic‐influenced environments. High levels of CH3CN were observed with minor biomass burning impact but still followed a similar correlation with carbon monoxide (CO), suggesting their shared source, most likely, vehicular emission. By analyzing the available literature including more than 30 worldwide field measurements, the enhancement ratios (EnRs) of CH3CN to CO for biomass burning were found as 2.01 ± 0.16 ppbv/ppmv, well distinguished from the EnRs obtained in urban measurement (0.26 ± 0.04 ppbv/ppmv). An example is given and the application of EnR to identify biomass burning is discussed. The results suggest that the correlation between CH3CN and CO and their EnRs can be used as more specific indicators for biomass burning.
Consistent Predictability of the Ocean State Ocean Model Using Information Theory and Flushing Timescales
Authors: Sane Aakash , Fox‐Kemper Baylor , Ullman David S. , Kincaid Christopher , Rothstein Lewis
Published: June 2021

The Ocean State Ocean Model (OSOM) is an application of the Regional Ocean Modeling System spanning the Rhode Island waterways, including Narragansett Bay, Mt. Hope Bay, larger rivers, and the Block Island Shelf circulation from Long Island to Nantucket. This study discusses the physical aspects of the estuary (Narragansett and Mount Hope Bays and larger rivers) to evaluate physical circulation predictability. This estimate is intended to help decide if a forecast and prediction system is warranted, to prepare for coupling with biogeochemistry and fisheries models with widely disparate timescales, and to find the spin‐up time needed to establish the climatological circulation of the region. Perturbed initial condition ensemble simulations are combined with metrics from information theory to quantify the predictability of the OSOM forecast system–i.e., how long anomalies from different initial conditions persist. The predictability timescale in this model agrees with readily estimable timescales such as the freshwater flushing timescale evaluated using the total exchange flow (TEF) framework, indicating that the estuarine dynamics rather than chaotic transport is the dominant model behavior limiting predictions. The predictability of the OSOM is ∼7–40 days, varying with parameters, region, and season.
Chinese Word Segmentation Based on Self‐Learning Model and Geological Knowledge for the Geoscience Domain
Authors: Li Wenjia , Ma Kai , Qiu Qinjun , Wu Liang , Xie Zhong , Li Sanfeng , Chen Siqiong
Published: May 2021

Chinese word segmentation (CWS) is the foundational work of geological report text mining and has an important influence on various tasks, such as named entity recognition and relation extraction. In recent years, the accuracy of the domain‐general CWS model has been limited by the domain and large scale of the training corpus, especially data on Chinese geological texts. Training these CWS models also requires much manually annotated data, which takes a large amount of time and effort. When applying these existing models/methods directly to the geoscience domain, the segmentation accuracy and performance will drop dramatically. To address this problem, we pretrain the Bidirectional Encoder Representations from Transformer (BERT), which can leverage unlabeled domain‐specific knowledge, on unlabeled Chinese geological text and then input them into a Bidirectional long short‐term memory and Conditional random field (BiLSTM‐CRF) model for extracting text features. Finally, the predicted tags are decoded by the CRF. The experimental results show that the F1 score of the proposed model reaches 96.2% on the constructed test set of geological texts. Additionally, experiments illustrate that our proposed model achieves comparable performance to that of other state‐of‐the‐art models, and the proposed cyclic self‐learning strategy can be further extended to other domains.
High Fluid‐Pressure Patches Beneath the Décollement: A Potential Source of Slow Earthquakes in the Nankai Trough off Cape Muroto
Authors: Hirose T. , Hamada Y. , Tanikawa W. , Kamiya N. , Yamamoto Y. , Tsuji T. , Kinoshita M. , Heuer V. B. , Inagaki F. , Morono Y. , Kubo Y.
Published: May 2021

Pore pressure plays a key role in the generation of earthquakes in subduction zones. However, quantitative constraints for its determination are quite limited. Here, we estimate the subsurface pore pressure by analyzing the transient upwelling flow of drilling mud from borehole C0023A of the International Ocean Discovery Program (IODP) Expedition 370, in the Nankai Trough off Cape Muroto. This upward flow provided the first direct evidence of an overpressured aquifer in the underthrust sediments off Cape Muroto. To estimate the pre‐drilling pore pressure in the overpressured aquifer around a depth of 950–1,050 m below sea floor, we examined the measured porosities of core samples retrieved from nearby IODP wells; we then proceeded to explain the observed time evolution of the flow rate of the upwelling flow by modeling various sized aquifers through solving a radial diffusion equation. It was observed that for a permeability of 10−13 m2, the aquifer possessed an initial excess pore pressure of ∼5–10 MPa above the hydrostatic pressure, with a lateral dimension of several hundred meters and thickness of several tens of meters. The overpressure estimates from the porosity‐depth profile at Site C0023 differ from those at other drill sites in the region, suggesting the possible existence of multiple overpressured aquifers with a patchy distribution in the underthrust sediments of the Nankai Trough. As pore pressure is relevant in maintaining fault stability, the overpressured aquifers may be the source of slow earthquakes that have been observed around the drilling site.
Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators
Authors: Seo Jinho , Nam Young Woo , Kim Seongmi , Oh Doo-Byoung , Song Jaewhan
Published: June 2021

Necroptosis is a form of programmed necrosis that is mediated by various cytokines and pattern recognition receptors (PRRs). Cells dying by necroptosis show necrotic phenotypes, including swelling and membrane rupture, and release damage-associated molecular patterns (DAMPs), inflammatory cytokines, and chemokines, thereby mediating extreme inflammatory responses. Studies on gene knockout or necroptosis-specific inhibitor treatment in animal models have provided extensive evidence regarding the important roles of necroptosis in inflammatory diseases. The necroptosis signaling pathway is primarily modulated by activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates mixed-lineage kinase domain-like protein (MLKL), mediating MLKL oligomerization. In the necroptosis process, these proteins are fine-tuned by posttranslational regulation via phosphorylation, ubiquitination, glycosylation, and protein–protein interactions. Herein, we review recent findings on the molecular regulatory mechanisms of necroptosis.
STAT3 activation in large granular lymphocyte leukemia is associated with cytokine signaling and DNA hypermethylation
Authors: Kim Daehong , Park Giljun , Huuhtanen Jani , Ghimire Bishwa , Rajala Hanna , Moriggl Richard , Chan Wing C. , Kankainen Matti , Myllymäki Mikko , Mustjoki Satu
Published: June 2021

Large granular lymphocyte leukemia (LGLL) is characterized by somatic gain-of-function STAT3 mutations. However, the functional effects of STAT3 mutations on primary LGLL cells have not been studied in detail. In this study, we show that CD8+ T cells isolated from STAT3 mutated LGLL patients have high protein levels of epigenetic regulators, such as DNMT1, and are characterized by global hypermethylation. Correspondingly, treatment of healthy CD8+ T cells with IL-6, IL-15, and/or MCP-1 cytokines resulted in STAT3 activation, increased DNMT1, EZH2, c-MYC, l-MYC, MAX, and NFκB levels, increased DNA methylation, and increased oxidative stress. Similar results were discovered in KAI3 NK cells overexpressing gain-of-function STAT3Y640F and STAT3G618R mutants compared to KAI3 NK cells overexpressing STAT3WT. Our results also confirm that STAT3 forms a direct complex with DNMT1, EZH2, and HDAC1. In STAT3 mutated LGLL cells, DNA methyltransferase (DNMT) inhibitor azacitidine abrogated the activation of STAT3 via restored SHP1 expression. In conclusion, STAT3 mutations cause DNA hypermethylation resulting in sensitivity to DNMT inhibitors, which could be considered as a novel treatment option for LGLL patients with resistance to standard treatments.
Lithium increases mitochondrial respiration in iPSC-derived neural precursor cells from lithium responders
Authors: Osete Jordi Requena , Akkouh Ibrahim A. , de Assis Denis Reis , Szabo Attila , Frei Evgeniia , Hughes Timothy , Smeland Olav B. , Steen Nils Eiel , Andreassen Ole A. , Djurovic Srdjan
Published: June 2021

Lithium (Li), valproate (VPA) and lamotrigine (LTG) are commonly used to treat bipolar disorder (BD). While their clinical efficacy is well established, the mechanisms of action at the molecular level are still incompletely understood. Here we investigated the molecular effects of Li, LTG and VPA treatment in induced pluripotent stem cell (iPSC)-derived neural precursor cells (NPCs) generated from 3 healthy controls (CTRL), 3 affective disorder Li responsive patients (Li-R) and 3 Li non-treated patients (Li-N) after 6 h and 1 week of exposure. Differential expression (DE) analysis after 6 h of treatment revealed a transcriptional signature that was associated with all three drugs and most significantly enriched for ribosome and oxidative phosphorylation (OXPHOS) pathways. In addition to the shared DE genes, we found that Li exposure was associated with 554 genes uniquely regulated in Li-R NPCs and enriched for spliceosome, OXPHOS and thermogenesis pathways. In-depth analysis of the treatment-associated transcripts uncovered a significant decrease in intron retention rate, suggesting that the beneficial influence of these drugs might partly be related to splicing. We examined the mitochondrial respiratory function of the NPCs by exploring the drugs’ effects on oxygen consumption rate (OCR) and glycolytic rate (ECAR). Li improved OCR levels only in Li-R NPCs by enhancing maximal respiration and reserve capacity, while VPA enhanced maximal respiration and reserve capacity in Li-N NPCs. Overall, our findings further support the involvement of mitochondrial functions in the molecular mechanisms of mood stabilizers and suggest novel mechanisms related to the spliceosome, which warrant further investigation.
A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report
Authors: te Paske Iris B. A. W. , Garcia-Pelaez José , Sommer Anna K. , Matalonga Leslie , Starzynska Teresa , Jakubowska Anna ,   Solve-RD-GENTURIS group,, Valle Laura , Capella Gabriel , Aretz Stefan , Holinski-Feder Elke , Steinke-Lange Verena , Laner Andreas , Schröck Evelin , Rump Andreas , Ligtenberg Marjolijn , Hoischen Alexander , Geverink Nicoline , Evans D. Gareth , Tischkowitz Marc , Laurie Steven , van der Post Rachel S. , Lubinski Jan , Oliveira Carla , Hoogerbrugge Nicoline , de Voer Richarda M.
Published: June 2021

Hereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n = 83) identified a mosaic missense variant in PIK3CA in a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CA are usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC.
Sex-biased genes and metabolites explain morphologically sexual dimorphism and reproductive costs in Salix paraplesia catkins
Authors: Cai Zeyu , Yang Congcong , Liao Jun , Song Haifeng , Zhang Sheng
Published: June 2021

Dioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions. As reproductive organs, unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism. To date, little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers. We investigated male and female flowers ofSalix paraplesiain three flowering stages before pollination (the early, blooming and late stages) via transcriptional sequencing as well as metabolite content and phenotypic analysis. We found that a large number of sex-biased genes, rather than sex-limited genes, were responsible for sexual dimorphism inS. paraplesiaflowers and that the variation in gene expression in male flowers intensified this situation throughout flower development. The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages. Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes. These sex-biased genes were involved mainly in signal transduction, photosynthesis, respiration, cell proliferation, phytochrome biosynthesis, and phenol metabolism; therefore, they resulted in more biomass accumulation and higher energy consumption in male catkins. Our results indicated that sex-biased gene expression inS. paraplesiaflowers is associated with different reproductive investments in unisexual flowers; male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.
Advances and perspectives in discovery and functional analysis of small secreted proteins in plants
Authors: Hu Xiao-Li , Lu Haiwei , Hassan Md Mahmudul , Zhang Jin , Yuan Guoliang , Abraham Paul E. , Shrestha Him K. , Villalobos Solis Manuel I. , Chen Jin-Gui , Tschaplinski Timothy J. , Doktycz Mitchel J. , Tuskan Gerald A. , Cheng Zong-Ming , Yang Xiaohan
Published: June 2021

Small secreted proteins (SSPs) are less than 250 amino acids in length and are actively transported out of cells through conventional protein secretion pathways or unconventional protein secretion pathways. In plants, SSPs have been found to play important roles in various processes, including plant growth and development, plant response to abiotic and biotic stresses, and beneficial plant–microbe interactions. Over the past 10 years, substantial progress has been made in the identification and functional characterization of SSPs in several plant species relevant to agriculture, bioenergy, and horticulture. Yet, there are potentially a lot of SSPs that have not been discovered in plant genomes, which is largely due to limitations of existing computational algorithms. Recent advances in genomics, transcriptomics, and proteomics research, as well as the development of new computational algorithms based on machine learning, provide unprecedented capabilities for genome-wide discovery of novel SSPs in plants. In this review, we summarize known SSPs and their functions in various plant species. Then we provide an update on the computational and experimental approaches that can be used to discover new SSPs. Finally, we discuss strategies for elucidating the biological functions of SSPs in plants.
EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing T helper cells
Authors: Roy Suyasha , Rizvi Zaigham Abbas , Clarke Alexander J. , Macdonald Felicity , Pandey Abhaydeep , Zaiss Dietmar Martin Werner , Simon Anna Kathrina , Awasthi Amit
Published: June 2021

Interleukin 9 (IL-9)-producing helper T (Th9) cells are essential for inducing anti-tumor immunity and inflammation in allergic and autoimmune diseases. Although transcription factors that are essential for Th9 cell differentiation have been identified, other signaling pathways that are required for their generation and functions are yet to be explored. Here, we identify that Epidermal Growth Factor Receptor (EGFR) is essential for IL-9 induction in helper T (Th) cells. Moreover, amphiregulin (Areg), an EGFR ligand, is critical for the amplification of Th9 cells induced by TGF-β1 and IL-4. Furthermore, our data show that Areg-EGFR signaling induces HIF1α, which binds and transactivates IL-9 and NOS2 promoters in Th9 cells. Loss of EGFR or HIF1α abrogates Th9 cell differentiation and suppresses their anti-tumor functions. Moreover, in line with its reliance on HIF1α expression, metabolomics profiling of Th9 cells revealed that Succinate, a TCA cycle metabolite, promotes Th9 cell differentiation and Th9 cell-mediated tumor regression.
Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle
Authors: Betrie Ashenafi H. , Brock James A. , Harraz Osama F. , Bush Ashley I. , He Guo-Wei , Nelson Mark T. , Angus James A. , Wright Christine E. , Ayton Scott
Published: June 2021

Zinc, an abundant transition metal, serves as a signalling molecule in several biological systems. Zinc transporters are genetically associated with cardiovascular diseases but the function of zinc in vascular tone regulation is unknown. We found that elevating cytoplasmic zinc using ionophores relaxed rat and human isolated blood vessels and caused hyperpolarization of smooth muscle membrane. Furthermore, zinc ionophores lowered blood pressure in anaesthetized rats and increased blood flow without affecting heart rate. Conversely, intracellular zinc chelation induced contraction of selected vessels from rats and humans and depolarized vascular smooth muscle membrane potential. We demonstrate three mechanisms for zinc-induced vasorelaxation: (1) activation of transient receptor potential ankyrin 1 to increase calcitonin gene-related peptide signalling from perivascular sensory nerves; (2) enhancement of cyclooxygenase-sensitive vasodilatory prostanoid signalling in the endothelium; and (3) inhibition of voltage-gated calcium channels in the smooth muscle. These data introduce zinc as a new target for vascular therapeutics.
Flavin-dependent halogenases catalyze enantioselective olefin halocyclization
Authors: Mondal Dibyendu , Fisher Brian F. , Jiang Yuhua , Lewis Jared C.
Published: June 2021

Halocyclization of alkenes is a powerful bond-forming tool in synthetic organic chemistry and a key step in natural product biosynthesis, but catalyzing halocyclization with high enantioselectivity remains a challenging task. Identifying suitable enzymes that catalyze enantioselective halocyclization of simple olefins would therefore have significant synthetic value. Flavin-dependent halogenases (FDHs) catalyze halogenation of arene and enol(ate) substrates. Herein, we reveal that FDHs engineered to catalyze site-selective aromatic halogenation also catalyze non-native bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Highly selective halocyclization is achieved by characterizing and mitigating the release of HOBr from the FDH active site using a combination of reaction optimization and protein engineering. The structural origins of improvements imparted by mutations responsible for the emergence of halocyclase activity are discussed. This expansion of FDH catalytic activity presages the development of a wide range of biocatalytic halogenation reactions.
Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay
Authors: Cai Aijie , Yan Wenhao , Zeng Xiaojun , Zacate Samson B. , Chao Tzu-Hsuan , Krause Jeanette A. , Cheng Mu-Jeng , Liu Wei
Published: June 2021

Organic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis in a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This approach simultaneously introduces CF2H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF2H radical addition. We demonstrate a broad substrate scope and a wide functional group compatibility. This scalable protocol is applied to the late-stage functionalization of complex molecules and the synthesis of CF2H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF2H species.
A novel ferroptosis related gene signature is associated with prognosis in patients with ovarian serous cystadenocarcinoma
Authors: Yu Zhixiang , He Haiyan , Chen Yanan , Ji Qiuhe , Sun Min
Published: June 2021

Ovarian cancer (OV) is a common type of carcinoma in females. Many studies have reported that ferroptosis is associated with the prognosis of OV patients. However, the mechanism by which this occurs is not well understood. We utilized Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) to identify ferroptosis-related genes in OV. In the present study, we applied Cox regression analysis to select hub genes and used the least absolute shrinkage and selection operator to construct a prognosis prediction model with mRNA expression profiles and clinical data from TCGA. A series of analyses for this signature was performed in TCGA. We then verified the identified signature using International Cancer Genome Consortium (ICGC) data. After a series of analyses, we identified six hub genes (DNAJB6, RB1, VIMP/ SELENOS, STEAP3, BACH1, and ALOX12) that were then used to construct a model using a training data set. The model was then tested using a validation data set and was found to have high sensitivity and specificity. The identified ferroptosis-related hub genes might play a critical role in the mechanism of OV development. The gene signature we identified may be useful for future clinical applications.
High-throughput phenotyping methods for quantifying hair fiber morphology
Authors: Lasisi Tina , Zaidi Arslan A. , Webster Timothy H. , Stephens Nicholas B. , Routch Kendall , Jablonski Nina G. , Shriver Mark D.
Published: June 2021

Quantifying the continuous variation in human scalp hair morphology is of interest to anthropologists, geneticists, dermatologists and forensic scientists, but existing methods for studying hair form are time-consuming and not widely used. Here, we present a high-throughput sample preparation protocol for the imaging of both longitudinal (curvature) and cross-sectional scalp hair morphology. Additionally, we describe and validate a new Python package designed to process longitudinal and cross-sectional hair images, segment them, and provide measurements of interest. Lastly, we apply our methods to an admixed African-European sample (n = 140), demonstrating the benefit of quantifying hair morphology over classification, and providing evidence that the relationship between cross-sectional morphology and curvature may be an artefact of population stratification rather than a causal link.
Comparative analysis of the gut microbiota of mice fed a diet supplemented with raw and cooked beef loin powder
Authors: Kim Hye-Jin , Kim Dongwook , Kim Kwan-Woo , Lee Sang-Hoon , Jang Aera
Published: June 2021

We used 16S ribosomal RNA sequencing to evaluate changes in the gut microbiota of mice fed a diet supplemented with either raw or cooked beef loin powder for 9 weeks. Male BALB/c mice (n = 60) were randomly allocated to five groups: mice fed AIN-93G chow (CON), chow containing 5% (5RB) and 10% (10RB) raw beef loin powder, and chow containing 5% (5CB) and 10% (10CB) cooked beef loin powder. Dietary supplementation with both RB and CB increased the relative abundance of Clostridiales compared to the CON diet (p < 0.05). Mice fed 10RB showed a significantly higher relative abundance of Firmicutes (p = 0.018) and Lactobacillus (p = 0.001) than CON mice, and the ratio of Firmicutes/Bacteroidetes showed an increasing trend in the 10RB mice (p > 0.05). Mice fed 10CB showed a higher abundance of Peptostreptococcaceae and a lower abundance of Desulfovibrionaceae compared with the CON mice (p < 0.05). Genes for glycan biosynthesis, which result in short-chain fatty acid synthesis, were enriched in the CB mice compared to the RB mice, which was correlated to a high abundance of Bacteroides. Overall, dietary RB and CB changed the gut microbiota of mice (p < 0.05).
Differentiation between non-small cell lung cancer and radiation pneumonitis after carbon-ion radiotherapy by 18F-FDG PET/CT texture analysis
Authors: Suga Makito , Nishii Ryuichi , Miwa Kenta , Kamitaka Yuto , Yamazaki Kana , Tamura Kentaro , Yamamoto Naoyoshi , Kohno Ryosuke , Kobayashi Masato , Tanimoto Katsuyuki , Tsuji Hiroshi , Higashi Tatsuya
Published: June 2021

The differentiation of non-small cell lung cancer (NSCLC) and radiation pneumonitis (RP) is critically essential for selecting optimal clinical therapeutic strategies to manage post carbon-ion radiotherapy (CIRT) in patients with NSCLC. The aim of this study was to assess the ability of 18F-FDG PET/CT metabolic parameters and its textural image features to differentiate NSCLC from RP after CIRT to develop a differential diagnosis of malignancy and benign lesion. We retrospectively analyzed 18F-FDG PET/CT image data from 32 patients with histopathologically proven NSCLC who were scheduled to undergo CIRT and 31 patients diagnosed with RP after CIRT. The SUV parameters, metabolic tumor volume (MTV), total lesion glycolysis (TLG) as well as fifty-six texture parameters derived from seven matrices were determined using PETSTAT image-analysis software. Data were statistically compared between NSCLC and RP using Wilcoxon rank-sum tests. Diagnostic accuracy was assessed using receiver operating characteristics (ROC) curves. Several texture parameters significantly differed between NSCLC and RP (p < 0.05). The parameters that were high in areas under the ROC curves (AUC) were as follows: SUVmax, 0.64; GLRLM run percentage, 0.83 and NGTDM coarseness, 0.82. Diagnostic accuracy was improved using GLRLM run percentage or NGTDM coarseness compared with SUVmax (p < 0.01). The texture parameters of 18F-FDG uptake yielded excellent outcomes for differentiating NSCLC from radiation pneumonitis after CIRT, which outperformed SUV-based evaluation. In particular, GLRLM run percentage and NGTDM coarseness of 18F-FDG PET/CT images would be appropriate parameters that can offer high diagnostic accuracy.
Benthic estuarine communities' contribution to bioturbation under the experimental effect of marine heatwaves
Authors: Dolbeth M. , Babe O. , Costa D. A. , Mucha A. P. , Cardoso P. G. , Arenas F.
Published: June 2021

Marine heatwaves are increasing worldwide, with several negative impacts on biological communities and ecosystems. This 24-day study tested heatwaves' effect with distinct duration and recovery periods on benthic estuarine communities' diversity and contribution to ecosystem functioning experimentally. The communities were obtained from a temperate estuary, usually subjected to high daily thermal amplitudes. Our goal was to understand the communities' response to the thermal change, including the community descriptors and behavioural changes expected during heat extremes. We measured community composition and structural changes and the bioturbation process and nutrient release as ecosystem functioning measurements. Overall, our findings highlight the potential tolerance of studied estuarine species to the temperature ranges tested in the study, as community composition and structure were similar, independently of the warming effect. We detected a slight trend for bioturbation and nutrient release increase in the communities under warming, yet these responses were not consistent with the heatwaves exposure duration. Overall, we conclude on the complexity of estuarine communities’ contribution to functioning under warming, and the importance of scalable experiments with benthic organisms' responses to climate variability, accommodating longer time scales and replication. Such an approach would set more efficient expectations towards climate change mitigation or adaptation in temperate estuarine ecosystems.
Combined bio-chemical fertilizers ameliorate agro-biochemical attributes of black cumin (Nigella sativa L.)
Authors: Moradzadeh Samira , Siavash Moghaddam Sina , Rahimi Amir , Pourakbar Latifeh , Sayyed R. Z.
Published: May 2021

Nigella sativaL. is a medicinal plant with extensive, nutritional, pharmaceutical, and health applications. Nowadays, reducing the application of chemical fertilizers (synthetic fertilizers) is one of the main goals of sustainable agriculture to allow the production of safe crops. Therefore, the combined effect of urea and biofertilizers was studied on the quantitative and qualitative traits ofN. sativaL. in a randomized complete block design with 10 treatments and three replications. The treatments included control (no fertilization), U (100% chemical fertilizer as urea at 53.3 kg ha−1, Nb (Biofertilizer, Azotobacter vinelandii), Pb (Biofertilizer, Pantoea agglomerans and Pseudomonas putida), Kb (Biofertilizer, Bacillus spp.), NPKb (NPK, biofertilizer), Nb + 50% U, Pb + 50% U, Kb + 50%U and NPKb + 50% U. The NPK(b) + U50% was related to the highest quantity of plant height, branch diameter, capsule (follicle) number per plant, auxiliary branches, seed yield per plant, thousand-seed weight, essential oil content, total phenolic compounds, flavonoid content, DPPH free radical scavenging, nitric oxide (NO) radical scavenging, superoxide radical scavenging, chain-breaking activity, phosphorus content, and potassium content, along with U for the highest biological yield and (Pb) + U50% for the highest essential oil percentage which is close to (NPKb) + U50%. The lowest value was observed in all traits related to the control treatment except for branch diameter that was related to (NPKb). Hence, the application of (NPKb) + U50% as bio-chemical fertilizers improvedN. sativaL. Traits, so it can be recommended.
The heavy chain of 4F2 antigen promote prostate cancer progression via SKP-2
Authors: Maimaiti Maihulan , Sakamoto Shinichi , Sugiura Masahiro , Kanesaka Manato , Fujimoto Ayumi , Matsusaka Keisuke , Xu Minhui , Ando Keisuke , Saito Shinpei , Wakai Ken , Imamura Yusuke , Nakayama Keiichi , Kanai Yoshikatsu , Kaneda Atsushi , Ikehara Yuzuru , Ikeda Jun-Ichiro , Anzai Naohiko , Ichikawa Tomohiko
Published: June 2021

The 4F2 cell-surface antigen heavy chain (4F2hc) forms a heterodimeric complex with L-type amino acid transporter 1 (LAT1) and transports large neutral essential amino acids. However, in contrast to the traditional role of LAT1 in various cancers, the role of 4F2hc has largely remained unknown. The role of 4F2hc in prostate cancer was studied. Treatment of C4-2 cells with si4F2hc was found to suppress cellular growth, migratory and invasive abilities, with this effect occurring through the cell cycle, with a significant decrease in S phase and a significant increase in G0/G1 phase, suggesting cell cycle arrest. In addition, it was proven by RNA seq that the key to 4F2hc’s impact on cancer is SKP2. si4F2hc upregulates the protein expression of cyclin-dependent kinase inhibitors (P21cip1, P27kip1) through the downstream target SKP2. Furthermore, the expression of 4F2hc and LAT1 in prostate cancer cells suggests the importance of 4F2hc. Multivariate analysis showed that high 4F2hc expression was an independent prognostic factor for progression-free survival (HR 11.54, p = 0.0357). High 4F2hc was related to the clinical tumour stage (p = 0.0255) and Gleason score (p = 0.0035). Collectively, 4F2hc contributed significantly to prostate cancer (PC) progression. 4F2hc may be a novel marker and therapeutic target in PC.
Output of a valveless Liebau pump with biologically relevant vessel properties and compression frequencies
Authors: Davtyan Rubina , Sarvazyan Narine A.
Published: June 2021

Liebau pump is a tubular, non-peristaltic, pulsatile pump capable of creating unidirectional flow in the absence of valves. It requires asymmetrical positioning of the pincher relative to the attachment sites of its elastic segment to the rest of the circuit. Biological feasibility of such valveless pumps remains a hotly debated topic. To test the feasibility of the Liebau-based pumping in vessels with biologically relevant properties we quantified the output of Liebau pumps with their  compliant segments made of a silicone rubber that mimicked the Young modulus of soft tissues. The lengths, the inner diameters, thicknesses of the tested compliant segments ranged from 1 to 5 cm, 3 to 8 mm and 0.3 to 1 mm, respectively. The compliant segment of the setup was compressed at 0.5–2.5 Hz frequencies using a 3.5-mm-wide rectangular piston. A nearest-neighbor tracking algorithm was used to track movements of 0.5-mm carbon particles within the system. The viscosity of the aqueous solution was varied by increased percentage of glycerin. Measurements yielded quantitative relationships between viscosity, frequency of compression and the net flowrate. The use of the Liebau principle of valveless pumping in conjunction with physiologically sized vessel and contraction frequencies yields flowrates comparable to peristaltic pumps of the same dimensions. We conclude that the data confirm physiological feasibility of Liebau-based pumping and warrant further testing of its mechanism using excised biological conduits or tissue engineered components. Such biomimetic pumps can serve as energy-efficient flow generators in microdevices or to study the function of embryonic heart during its normal development or in diseased states.
A time-dependent parameter estimation framework for crop modeling
Authors: Akhavizadegan Faezeh , Ansarifar Javad , Wang Lizhi , Huber Isaiah , Archontoulis Sotirios V.
Published: June 2021

The performance of crop models in simulating various aspects of the cropping system is sensitive to parameter calibration. Parameter estimation is challenging, especially for time-dependent parameters such as cultivar parameters with 2–3 years of lifespan. Manual calibration of the parameters is time-consuming, requires expertise, and is prone to error. This research develops a new automated framework to estimate time-dependent parameters for crop models using a parallel Bayesian optimization algorithm. This approach integrates the power of optimization and machine learning with prior agronomic knowledge. To test the proposed time-dependent parameter estimation method, we simulated historical yield increase (from 1985 to 2018) in 25 environments in the US Corn Belt with APSIM. Then we compared yield simulation results and nine parameter estimates from our proposed parallel Bayesian framework, with Bayesian optimization and manual calibration. Results indicated that parameters calibrated using the proposed framework achieved an 11.6% reduction in the prediction error over Bayesian optimization and a 52.1% reduction over manual calibration. We also trained nine machine learning models for yield prediction and found that none of them was able to outperform the proposed method in terms of root mean square error and R2. The most significant contribution of the new automated framework for time-dependent parameter estimation is its capability to find close-to-optimal parameters for the crop model. The proposed approach also produced explainable insight into cultivar traits’ trends over 34 years (1985–2018).
Dual interleukin-17A/F deficiency protects against acute and chronic response to cigarette smoke exposure in mice
Authors: Wada Hiroo , Nakamura Masuo , Inoue Shin-Ichi , Kudo Akihiko , Hanawa Tomoko , Iwakura Yoichiro , Kobayashi Fumie , Kamma Hiroshi , Kamiya Shigeru , Ito Kazuhiro , Barnes Peter J. , Takizawa Hajime
Published: June 2021

IL-17A and IL-17F are both involved in the pathogenesis of neutrophilic inflammation observed in COPD and severe asthma. To explore this, mice deficient in bothIl17aandIl17fand wild type (WT) mice were exposed to cigarette smoke or environmental air for 5 to 28 days and changes in inflammatory cells in bronchoalveolar lavage (BAL) fluid were determined. We also measured the mRNA expression of keratinocyte derived chemokine (Kc), macrophage inflammatory protein-2 (Mip2), granulocyte–macrophage colony stimulating factor (Gmcsf)and matrix metalloproteinase-9 (Mmp9) in lung tissue after 8 days, and lung morphometric changes after 24 weeks of exposure to cigarette smoke compared to air-exposed control animals. Macrophage counts in BAL fluid initially peaked at day 8 and again on day 28, while neutrophil counts peaked between day 8 and 12 in WT mice. Mice dual deficient withIl17a and 1l17fshowed similar kinetics with macrophages and neutrophils, but cell numbers at day 8 and mRNA expression ofKc,GmcsfandMmp9were significantly reduced. Furthermore, airspaces in WT mice became larger after cigarette smoke exposure for 24 weeks, whereas this was not seen dualIl17a and 1l17fdeficient mice. CombinedIl17aandIl17fdeficiency resulted in significant attenuation of neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure compared with WT mice. Dual IL-17A/F signalling plays an important role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure.
Electrically controllable active plasmonic directional coupler of terahertz signal based on a periodical dual grating gate graphene structure
Authors: Morozov Mikhail Yu. , Popov Vyacheslav V. , Fateev Denis V.
Published: June 2021

We propose a concept of an electrically controllable plasmonic directional coupler of terahertz signal based on a periodical structure with an active (with inversion of the population of free charge carriers) graphene with a dual grating gate and numerically calculate its characteristics. Proposed concept of plasmon excitation by using the grating gate offers highly effective coupling of incident electromagnetic wave to plasmons as compared with the excitation of plasmons by a single diffraction element. The coefficient which characterizes the efficiency of transformation of the electromagnetic wave into the propagating plasmon has been calculated. This transformation coefficient substantially exceeds the unity (exceeding 6 in value) due to amplification of plasmons in the studied structure by using pumped active graphene. We have shown that applying different dc voltages to different subgratings of the dual grating gate allows for exciting the surface plasmon in graphene, which can propagate along or opposite the direction of the structure periodicity, or can be a standing plasma wave for the same frequency of the incident terahertz wave. The coefficient of unidirectionality, which is the ratio of the plasmon power flux propagating along (opposite) the direction of the structure periodicity to the sum of the absolute values of plasmon power fluxes propagating in both directions, could reach up to 80 percent. Two different methods of the plasmon propagation direction switching are studied and possible application of the found effects are suggested.
Cascaded processing enables continuous upstream processing with E. coli BL21(DE3)
Authors: Kittler Stefan , Slouka Christoph , Pell Andreas , Lamplot Roman , Besleaga Mihail , Ablasser Sarah , Herwig Christoph , Spadiut Oliver , Kopp Julian
Published: June 2021

In many industrial sectors continuous processing is already the golden standard to maximize productivity. However, when working with living cells, subpopulation formation causes instabilities in long-term cultivations. In cascaded continuous cultivation, biomass formation and recombinant protein expression can be spatially separated. This cultivation mode was found to facilitate stable protein expression using microbial hosts, however mechanistic knowledge of this cultivation strategy is scarce. In this contribution we present a method workflow to reduce workload and accelerate the establishment of stable continuous processes with E. coli BL21(DE3) exclusively based on bioengineering methods.
Fewer bat passes are detected during small, commercial drone flights
Authors: Ednie Gabrielle , Bird David M. , Elliott Kyle H.
Published: June 2021

Advances in technological capabilities, operational simplicity and cost efficiency have promoted the rapid integration of unmanned aerial vehicles (UAVs) into ecological research, providing access to study taxa that are otherwise difficult to survey, such as bats. Many bat species are currently at risk, but accurately surveying populations is challenging for species that do not roost in large aggregations. Acoustic recorders attached to UAVs provide an opportunity to survey bats in challenging habitats. However, UAVs may alter bat behaviour, leading to avoidance of the UAV, reduced detection rates and inaccurate surveys. We evaluated the number of bat passes detected with and without the presence of a small, commercial UAV in open habitats. Only 22% of bat passes were recorded in the presence of the UAV (0.23 ± 0.09 passes/min) compared to control periods without the UAV (1.03 ± 0.17 passes/min), but the effect was smaller on the big brown bat/silver-haired bat (Eptesicus fuscus/Lasionycteris noctivagans) acoustic complex. Noise interference from the UAV also reduced on-board bat detection rates. We conclude that acoustic records attached to UAVs may inaccurately survey bat populations due to low and variable detection rates by such recorders.
Comparative analyses of transcriptional responses of Dectes texanus LeConte (Coleoptera: Cerambycidae) larvae fed on three different host plants and artificial diet
Authors: Aguirre-Rojas Lina M. , Scully Erin D. , Trick Harold N. , Zhu Kun Yan , Smith C. Michael
Published: June 2021

Dectes texanus is an important coleopteran pest of soybeans and cultivated sunflowers in the Midwestern United States that causes yield losses by girdling stems of their host plants. Although sunflower and giant ragweed are primary hosts of D. texanus, they began colonizing soybeans approximately 50 years ago and no reliable management method has been established to prevent or reduce losses by this pest. To identify genes putatively involved when feeding soybean, we compared gene expression of D. texanus third-instar larvae fed soybean to those fed sunflower, giant ragweed, or artificial diet. Dectes texanus larvae differentially expressed 514 unigenes when fed on soybean compared to those fed the other diet treatments. Enrichment analyses of gene ontology terms from up-regulated unigenes in soybean-fed larvae compared to those fed both primary hosts highlighted unigenes involved in oxidoreductase and polygalacturonase activities. Cytochrome P450s, carboxylesterases, major facilitator superfamily transporters, lipocalins, apolipoproteins, glycoside hydrolases 1 and 28, and lytic monooxygenases were among the most commonly up-regulated unigenes in soybean-fed larvae compared to those fed their primary hosts. These results suggest that D. texanus larvae differentially expressed unigenes involved in biotransformation of allelochemicals, digestion of plant cell walls and transport of small solutes and lipids when feeding in soybean.