bluuebunny/crossref_metadata_2025 huggingface dataset:
Organization and composition of apicomplexan kinetochores reveal plasticity in chromosome segregation across parasite modes of division
Authors: Brusini Lorenzo , Santos Pacheco Nicolas Dos , Soldati-Favre Dominique , Brochet Mathieu
Published: November 2021

Kinetochores are multiprotein assemblies directing mitotic spindle attachment and chromosome segregation. In apicomplexan parasites, most known kinetochore components and associated regulators are apparently missing, suggesting a minimal structure with limited control over chromosome segregation. In this study, we use interactomics combined with deep homology searches to identify six divergent eukaryotic components, in addition to a set of eight apicomplexan kinetochore proteins (AKiTs) that bear no detectable sequence similarity to known proteins. The nanoscale organization of the apicomplexan kinetochore includes four subdomains, each displaying different evolutionary rates across the phylum. Functional analyses confirm AKiTs are essential for mitosis and reveal architectures parallel to biorientation at metaphase. Furthermore, we identify a homolog of MAD1 at the apicomplexan kinetochore, suggesting conserved spindle assembly checkpoint signaling. Finally, we show unexpected plasticity in kinetochore composition and segregation throughout the parasite lifecycle, indicating diverse requirements to maintain fidelity of chromosome segregation across apicomplexan modes of division.
Challenging the notion of a task-negative network: default mode network involvement under varying levels of cognitive effort
Authors: Weber Sarah , Aleman André , Hugdahl Kenneth
Published: November 2021

Everyday cognitive functioning is characterized by constant alternations between different modes of information processing, driven by fluctuations in environmental demands. At the neural level, this is realized through corresponding dynamic shifts in functional activation and network connectivity. A distinction is often made between the Default Mode Network (DMN) as a task-negative network that is upregulated in the absence of cognitive demands, and task-positive networks that are upregulated when cognitive demands such as attention and executive control are present. Such networks have been labelled the Extrinsic Mode Network (EMN). We investigated changes in brain activation and functional network connectivity during repeated alternations between levels of cognitive effort. Using fMRI and a block-design Stroop paradigm, participants switched back and forth between periods of no effort (resting), low effort (word reading, automatic processing) and high effort (color naming, cognitive control). Results showed expected EMN-activation for task versus rest, and likewise expected DMN-activation for rest versus task. The DMN was also more strongly activated during low effort contrasted with high effort, suggesting a gradual up- and down-regulation of the DMN, depending on the level of demand. The often reported “anti-correlation” between DMN and EMN was only present during periods of low effort, indicating intermittent contributions of both networks. These results challenge the traditional view of the DMN as solely a task-negative network. Instead, the present results suggest that both EMN and DMN may contribute to low-effort cognitive processing. In contrast, periods of resting and high effort are dominated by the DMN and EMN, respectively.
Significant Subgraph Mining for Neural Network Inference with Multiple Comparisons Correction
Authors: Gutknecht Aaron J. , Wibral Michael
Published: November 2021

We describe how the recently introduced method of significant subgraph mining can be employed as a useful tool in network comparison. It is applicable whenever the goal is to compare two sets of unweighted graphs and to determine differences in the processes that generate them. We provide an extension of the method to dependent graph generating processes as the occur for example in within-subject experimental designs. Furthermore, we present an extensive investigation of error-statistical properties of the method in simulation using Erdős-Rényi models and in empirical data. In particular, we perform an empirical power analysis for transfer entropy networks inferred from resting state MEG data comparing autism spectrum patients with neurotypical controls. From this analysis one may estimate that the appropriate sample size for similar studies should be chosen in the order of n=60 per group or larger.

Author summary

A key objective of neuroscientifc research is to determine how different parts of the brain are connected. The end result of such investigations is always a graph consisting of nodes corresponding to brain regions or nerve cells and edges between the nodes indicating if they are connected or not. The connections may be structural (an actual anatomical connection) but can also be functional – meaning that there is a statistical dependency between the activity in one part of the brain and the activity in another. A prime example of the latter type of connection would be the information flow between brain areas. Differences in the patterns of connectivity are likely to be responsible for and indicative of various neurological disorders such as autism spectrum disorders. It is therefore important that efficient methods to detect such differences are available. The key problem in developing methods for comparing patterns of connectivity is that there is generally a vast number of different patterns (it can easily exceed the number of stars in the milky way). In this paper we describe how the recently developed method of significant subgraph mining accounts for this problem and how it can be usefully employed in neuroscientifc research.
Nicotinic modulation insecticides act on diverse receptor subtypes with distinct subunit compositions
Authors: Lu Wanjun , Liu Zhihan , Fan Xinyu , Zhang Xinzhong , Qiao Xiaomu , Huang Jia
Published: November 2021

Insect nicotinic acetylcholine receptors (nAChRs) are ligand gated ion channels mainly expressed in the central nervous system of insects. They are the directed targets of nicotinic modulation insecticides including neonicotinoids, the most widely used insecticides in the world. However, the resistance development from pests and the negative impacts on the pollinators affect their applications and create demand for the alternatives. Thus, it is very important to understand the mode of action of these insecticides at the molecular level, which is actually unclear for more than 30 years. In this study, we systematically examined the susceptibility of ten Drosophila melanogaster nAChR subunits mutants against eleven nicotinic modulation insecticides. Our results showed that there are several subtypes of nAChRs with distinct subunits compositions that are responsible for the toxicity of different insecticides, respectively. At least three of them are the major molecular targets of seven structurally similar neonicotinoids in vivo. On the other hand, the spinosyns may exclusively act on the α6 homomeric nAChR but not any other heteromeric pentamers. Behavioral assays using thermogenetic tools further confirmed the bioassay results and support the idea that receptor activation rather than inhibition leads to the insecticidal effects of neonicotinoids. The present findings reveal native nAChR subunit interactions with various insecticides and have important implications for resistance management and the development of novel insecticides targeting this important ion channels.

Author Summary

The neonicotinoids and spinosyns make up about 27% of the insecticides by world market value. Novel insecticides like sulfoxaflor, flupyradifurone and triflumezopyrim are developed as alternatives due to the negative effects of neonicotinoids on pollinators. Although all act via insect nicotinic acetylcholine receptors, the mode of action is unclear. Our work shows that these insecticides act on diverse receptor subtypes with distinct subunit compositions. This finding could lead to the development of more selective insecticides to control pests with minimal effects on beneficial insects.
Cancer causes dysfunctional insulin signaling and glucose transport in a muscle-type specific manner
Authors: Raun Steffen H. , Knudsen Jonas Roland , Han Xiuqing , Jensen Thomas E. , Sylow Lykke
Published: November 2021

Metabolic dysfunction and insulin resistance are emerging as hallmarks of cancer and cachexia, and impair cancer prognosis. Yet, the molecular mechanisms underlying impaired metabolic regulation is not fully understood. To elucidate the mechanisms behind cancer-induced insulin resistance in muscle, we isolated extensor digitorum longus (EDL) and soleus muscles from Lewis Lung Carcinoma tumor-bearing mice. Three weeks after tumor inoculation, muscles were isolated and stimulated with or without a submaximal dose of insulin (1.5 nM). Glucose transport was measured using 2-[3H]Deoxy-Glucose and intramyocellular signaling was investigated using immunoblotting. In soleus muscles from tumor-bearing mice, insulin-stimulated glucose transport was abrogated concomitantly with abolished insulin-induced TBC1D4 and GSK3 phosphorylation. In EDL, glucose transport and TBC1D4 phosphorylation were not impaired in muscles from tumor-bearing mice, while AMPK signaling was elevated. Anabolic insulin signaling via phosphorylation of the mTORC1 targets, p70S6K thr389 and ribosomal-S6 ser235, were decreased by cancer in soleus muscle while increased or unaffected in EDL. In contrast, the mTOR substrate, pULK1 ser757, was reduced in both soleus and EDL by cancer. Hence, cancer causes considerable changes in skeletal muscle insulin signaling that is dependent of muscle-type, which could contribute to metabolic dysregulation in cancer. Thus, skeletal muscle could be a target for managing metabolism in cancer.

Highlights

Cancer abrogates insulin-stimulated glucose transport selectively in oxidative soleus muscle

Multiple TBC1D4 phosphorylation sites are reduced in cancer-associated muscle insulin resistance

Cancer leads to increased AMPK signaling in the glycolytic EDL muscle

Cancer alters anabolic insulin signaling in soleus and EDL muscle
A drug repurposing screen identifies altiratinib as a selective inhibitor of a key regulatory splicing kinase and a potential therapeutic for toxoplasmosis and malaria
Authors: Swale Christopher , Bellini Valeria , Bowler Matthew W. , Flore Nardella , Brenier-Pinchart Marie-Pierre , Cannella Dominique , Belmudes Lucid , Mas Caroline , Couté Yohann , Laurent Fabrice , Scherf Artur , Bougdour Alexandre , Hakimi Mohamed-Ali
Published: November 2021

Introductory paragraph

The apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that infect humans and animals and cause severe parasitic diseases. Available therapeutics against these devastating diseases are limited by suboptimal efficacy and frequent side effects, as well as the emergence and spread of resistance. Here, we use a drug repurposing strategy and identify altiratinib, a compound originally developed to treat glioblastoma, as a promising drug candidate with broad spectrum activity against apicomplexans. Altiratinib is parasiticidal and blocks the development of intracellular zoites in the nanomolar range and with a high selectivity index. We have identified TgPRP4K of T. gondii as the primary target of altiratinib by genetic target deconvolution, highlighting key residues within the kinase catalytic site that, when mutated, confer resistance to the drug. We have further elucidated the molecular basis of the inhibitory mechanism and species selectivity of altiratinib for TgPRP4K as well as for its P. falciparum counterpart PfCLK3. Our data also point to structural features critical for binding of the other PfCLK3 inhibitor, TCMDC-135051. Consistent with the role of this kinase family in splicing in a broad spectrum of eukaryotes, we have shown that altiratinib causes global disruption of splicing, primarily through intron retention in both T. gondii and P. falciparum. Thus, our data establish parasitic PRP4K/CLK3 as a promising pan-apicomplexan target whose repertoire of inhibitors can be expanded by the addition of altiratinib.
Estimating the Designability of Protein Structures
Authors: Pan Feng , Zhang Yuan , Liu Xiuwen , Zhang Jinfeng
Published: November 2021

The total number of amino acid sequences that can fold to a target protein structure, known as “designability”, is a fundamental property of proteins that contributes to their structure and function robustness. The highly designable structures always have higher thermodynamic stability, mutational stability, fast folding, regular secondary structures, and tertiary symmetries. Although it has been studied on lattice models for very short chains by exhaustive enumeration, it remains a challenge to estimate the designable quantitatively for real proteins. In this study, we designed a new deep neural network model that samples protein sequences given a backbone structure using sequential Monte Carlo method. The sampled sequences with proper weights were used to estimate the designability of several real proteins. The designed sequences were also tested using the latest AlphaFold2 and RoseTTAFold to confirm their foldabilities. We report this as the first study to estimate the designability of real proteins.
A survey ofcisregulatory non-coding RNA involved in bacterial virulence
Authors: Naghdi Mohammad Reza , Djerroud Samia , Smail Katia , Perreault Jonathan
Published: November 2021

Study of pathogenesis in bacteria is important to find new drug targets to treat bacterial infections. Pathogenic bacteria, including opportunists, express numerous so-called virulence genes to escape the host natural defenses and immune system. Regulation of virulence genes is often required for bacteria to infect their host. Such regulation can be achieved bycis-regulatory RNAs, like the metabolite-binding riboswitches or thermoregulators. In spite of the hundreds of RNA families annotated as cis-regulatory, there are relatively few examples of non-coding RNAs (ncRNAs) in 5′-UnTranslated Regions (UTRs) of bacteria described to regulate downstream virulence genes. To reassess the potential roles of such regulatory elements in bacterial pathogenesis, we collected genes important for virulence from different databases and evaluated the presence of ncRNAs in their UTRs to highlight the potential role of this type of gene regulation for virulence and, at the same time, get insight on some of the physical and chemical triggers of virulence.
A molecular network of conserved factors keeps ribosomes dormant in the egg
Authors: Leesch Friederike , Lorenzo-Orts Laura , Pribitzer Carina , Grishkovskaya Irina , Matzinger Manuel , Roitinger Elisabeth , Belačić Katarina , Kandolf Susanne , Lin Tzi-Yang , Mechtler Karl , Meinhart Anton , Haselbach David , Pauli Andrea
Published: November 2021

Ribosomes are produced in large quantities during oogenesis and stored in the egg. However, the egg and early embryo are translationally repressed. Using mass-spectrometry and cryo-EM analyses of ribosomes isolated from zebrafish and Xenopus eggs and embryos, we provide molecular evidence that ribosomes transition from a dormant to an active state during the first hours of embryogenesis. Dormant ribosomes are associated with four conserved factors that form two modules and occupy functionally important sites of the ribosome: a Habp4-eEF2 module that stabilizes ribosome levels and a Dap1b/Dapl1-eIF5a module that represses translation. Dap1b/Dapl1 is a newly discovered translational inhibitor that stably inserts into the polypeptide exit tunnel. Thus, a developmentally programmed, conserved ribosome state plays a key role in ribosome storage and translational repression in the egg.
Intact Drosophila Central Nervous System Cellular Quantitation reveals Sexual Dimorphism
Authors: Jiao Wei , Spreemann Gard , Ruchti Evelyne , Banerjee Soumya , Vernon Samuel , Shi Ying , Stowers R. Steven , Hess Kathryn , McCabe Brian D.
Published: November 2021

Establishing with precision the quantity and identity of the cell types of the brain is a prerequisite for a detailed compendium of gene and protein expression in the central nervous system. Currently however, strict quantitation of cell numbers has been achieved only for the nervous system ofC.elegans. Here we describe the development of a synergistic pipeline of molecular genetic, imaging, and computational technologies designed to allow high-throughput, precise quantitation with cellular resolution of reporters of gene expression in intact whole tissues with complex cellular constitutions such as the brain. We have deployed the approach to determine with exactitude the number of functional neurons and glia in the entire intact larvalDrosophilacentral nervous system (CNS), revealing fewer neurons and more glial cells than previously predicted. We also discover an unexpected divergence between the sexes at this juvenile developmental stage, with the female CNS having significantly more neurons than that of males. Topological analysis of our data establishes that this sexual dimorphism extends to deeper features of CNS organisation. We additionally extended our analysis to quantitate the expression of voltage-gated potassium channel family genes throughout the CNS and uncover substantial differences in abundance. Our methodology enables robust and accurate quantification of the number and positioning of cells within intact organs, facilitating sophisticated analysis of cellular identity, diversity, and gene expression characteristics.
Maternally-inherited anti-sense piRNAs antagonize transposon expression in teleost embryos
Authors: Guo Yixuan , Gert Krista R. , Lebedeva Svetlana , Potok Magdalena E. , Wike Candice L. , Grow Edward J. , Ketting René F. , Pauli Andrea , Cairns Bradley R.
Published: November 2021

Transposable elements threaten genome stability, and the Piwi-piRNA system has evolved to silence transposons in the germline1–6. However, it remains largely unknown what mechanisms are utilized in early vertebrate embryos prior to germline establishment and ‘ping-pong’ piRNA production. To address this, we first characterized small RNAs in early zebrafish embryos and detected abundant maternally-deposited, Ziwi-associated, antisense piRNAs that map largely to evolutionarily young long terminal repeat (LTR) retrotransposons. Notably, the focal establishment of the repressive modification H3K9me2/3 coincides with these young LTR elements, is deposited independent of transcription, and is required for LTR silencing. We find piRNAs highly enriched and maintained in primordial germ cells (PGCs), which display lower LTR expression than somatic cells. To examine the consequences of piRNA loss, we used reciprocal zebrafish-medaka hybrids, which display selective activation of LTRs that lack maternally-contributed targeting piRNAs. Thus, the Piwi-piRNA system actively antagonizes transposons in the soma and PGCs during early vertebrate embryogenesis.
Integrative Modelling of Signalling Network Dynamics Identifies Cell Type-selective Therapeutic Strategies for FGFR4-driven Cancers
Authors: Shin Sung-Young , Chew Nicole J , Ghomlaghi Milad , Chüeh Anderly C , Jeong Yunhui , Nguyen Lan K. , Daly Roger J
Published: November 2021

Oncogenic FGFR4 signalling represents a potential therapeutic target in various cancer types, including triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC). However, resistance to FGFR4 single-agent therapy remains a major challenge, emphasizing the need for effective combinatorial treatments. Our study sought to develop a comprehensive computational model of FGFR4 signalling and provide network-level insights into resistance mechanisms driven by signalling dynamics. Our integrated approach, combining computational network modelling with experimental validation, uncovered potent AKT reactivation following FGFR4 targeting in the TNBC cell line MDA-MB-453. By systematically simulating the model to analyse the effects of co-targeting specific network nodes, we were able to predict, and subsequently confirm through experimental validation, the strong synergy of co-targeting FGFR4 and AKT or specific ErbB kinases, but not PI3K. Incorporating protein expression data from hundreds of cancer cell lines, we then adapted our model to diverse cellular contexts. This revealed that while AKT rebound is common, it is not a general phenomenon. ERK reactivation, for example, occurs in certain cell types, including the FGFR4-driven HCC cell line Hep3B, where there is a synergistic effect of co-targeting FGFR4 and MEK, but not AKT. In summary, our study offers key insights into drug-induced network remodelling and the role of protein expression heterogeneity in targeted therapy responses. We underscore the utility of computational network modelling for designing cell type-selective combination therapies and enhancing precision cancer treatment.

Significance

This study underscores the potential of computational predictive modelling in deciphering mechanisms of cancer cell resistance to targeted therapies and in designing more effective, cancer type-specific combination treatments.
Distinct roles for CDK-Mediator in controlling Polycomb-dependent chromosomal interactions and priming genes for induction
Authors: Dimitrova Emilia , Feldmann Angelika , van der Weide Robin H. , Flach Koen D. , Lastuvkova Anna , de Wit Elzo , Klose Robert J.
Published: November 2021

Precise control of gene expression underpins normal development. This relies on mechanisms that enable communication between gene promoters and other regulatory elements. In embryonic stem cells (ESCs), the CDK-Mediator (CDK-MED) complex has been reported to physically link gene regulatory elements to enable gene expression and also prime genes for induction during differentiation. Here we discover that CDK-MED contributes little to 3D genome organisation in ESCs, but has a specific and essential role in controlling interactions between inactive gene regulatory elements bound by Polycomb repressive complexes (PRCs). These interactions are established by the canonical PRC1 (cPRC1) complex but rely on CDK-MED, which facilitates binding of cPRC1 to its target sites. Importantly, through separation of function experiments, we reveal that this collaboration between CDK-MED and cPRC1 in creating long-range interactions does not function to prime genes for induction during differentiation. Instead, we discover that priming relies on an interaction-independent mechanism whereby the CDK module supports core Mediator engagement with gene promoters to enable gene activation.
Dynamic spreading of chromatin-mediated gene silencing and reactivation between neighboring genes in single cells
Authors: Lensch Sarah , Herschl Michael H. , Ludwig Connor H. , Sinha Joydeb , Hinks Michaela M. , Mukund Adi , Fujimori Taihei , Bintu Lacramioara
Published: November 2021

In mammalian cells genes that are in close proximity are coupled transcriptionally: silencing or activating one gene can affect its neighbors. Understanding these dynamics is important for natural processes, such as heterochromatin spreading during development and aging, and when designing synthetic gene regulation. Here, we systematically dissect this process in single cells by recruiting and releasing repressive chromatin regulators at dual-gene synthetic reporters, and measuring how fast gene silencing and reactivation spread as a function of intergenic distance and configuration of insulator elements. We find that silencing by KRAB, associated with histone methylation, spreads between two genes within hours, with a time delay that increases with distance. This fast KRAB-mediated spreading is not blocked by the classical cHS4 insulators. Silencing by histone deacetylase HDAC4 of the upstream gene can also lead to downstream gene silencing, but with a days-long delay that does not change with distance. This slower silencing can sometimes be stopped by insulators. Gene reactivation of neighboring genes is also coupled, with strong promoters and insulators determining the order of reactivation. We propose a new model of multi-gene regulation, where both gene silencing and gene reactivation can act at a distance, allowing for coordinated dynamics via chromatin regulator recruitment.
Physical Internet deployment in industry: literature review and research opportunities
Authors: Chen Sihua , Su Linlin , Cheng Xusen
Published: November 2021

Purpose

The Physical Internet (PI) provides solutions to improve the current unsustainable economically logistics systems. This paper aims to identify the key themes and point out the gaps to demonstrate the current state of the PI deployment in the industry. Furthermore, this paper attempts to provide possible opportunities for future research to lead research directions of PI deployment in the industry.

Design/methodology/approach

This paper follows the methodology of systematic literature review (SLR) including five processes of (1) identifying the search process; (2) selecting publications following the criteria that include and/or exclude a publication; (3) evaluating and analyzing the chosen literature; (4) reporting findings and (5) synthesizing future research opportunities. A total of 88 papers ranging from 2011 to 2021 were selected and coded for analysis.

Findings

This paper has identified 7 themes, including the PI concepts, assessments of the PI, components of the PI, innovative facilities applied in the PI, collaboration in the PI, the PI implementation and literature review. Meanwhile, five key methodologies including experimental, exploratory, review, design science research as well as mixed-methods have been classified. A framework has been proposed to summarize the results incorporating the real-life industries involved in the existing research. The authors also present the research gaps and future research opportunities for the PI deployment in industries.

Originality/value

This study is one of the first research focusing on the PI real-life implementation and thus contributes to the PI literature differing from other literature review papers. The proposed framework is useful to learn about the current core research themes in the PI. The discussion of future research opportunities may inspire interesting research delving into the field.
Price and volume effects around Islamic index revisions: the case of DJIM-GCC
Authors: Labidi Chiraz , Laribi Dorra , Ureche-Rangau Loredana
Published: November 2021

Purpose

This study explores the price and trading volume effects around the quarterly Dow Jones Islamic Market-GCC index (DJIM-GCC) revisions and investigates whether these reactions are driven by firms' fundamentals or by investors' perception of ethical screening.

Design/methodology/approach

The authors adopt an event study methodology to analyze the price and volume effects of Islamic indices redefinitions.

Findings

The results exhibit a positive (negative) price reaction for added (deleted) stocks. The authors also document an asymmetric volume response for index additions and deletions. The multivariate analysis of the cumulative abnormal returns reveals that the documented market reaction around Islamic index revisions is mainly related to the compliance attribution (withdrawal).

Originality/value

The approach allows to separate the market reaction arising from changes in firms' fundamentals from that induced by investors' perception of the attribution or withdrawal of a compliance certification. Moreover, the focus on the GCC region, where countries share the same cultural traits and perceive Islamic law identically excludes any social effect that would influence the market reaction due to cultural differences between countries.
Unsupervised dual learning for seismic data denoising in the absence of labelled data
Authors: Zhao Yu Xing , Li Yue , Wu Ning
Published: November 2021

The training and updating of the supervised deep learning model are both dependent on labelled data. Unfortunately, the data‐labelling process is usually expensive and time consuming, which makes obtaining labelled data a huge challenge, especially in the field of geophysics. Because of the above‐mentioned factors, some seismic data denoising methods based on supervised deep learning use synthetic seismic data for network training. Since synthetic seismic data are more or less different from real seismic data, the denoising results may have some amount of residual noise and some false signals when dealing with real seismic data. In response to the above problems, this paper introduces an unpaired domain‐to‐domain translation method based on the framework of two‐way generative adversarial networks, which does not need to use labelled data for training, and effectively solves the problem of lacking labelled data in the seismic data denoising tasks. We use an unpaired mixed training set containing synthetic seismic data and real seismic data to train the network, which effectively improves the denoising ability of the network for the real seismic data. The experimental results show that compared with the state‐of‐the‐art denoising methods such as denoising convolutional neural network, the proposed method can suppress the random noise and ground roll more thoroughly, and the denoising results basically would have no false signals.
Late Quaternary Slip Behavior of the Jinqianghe Fault in the Middle Qilian–Haiyuan Fault Zone, Northeastern Tibetan Plateau
Authors: LIANG Shumin , ZHENG Wenjun , CHEN Gan , ZHANG Peizhen , ZHANG Dongli , BI Haiyun , YANG Xue , ZHANG Yipeng , DUAN Lei , LU Bentian
Published: November 2021

The Qilian–Haiyuan fault zone in the northeastern Tibetan Plateau has been the source of strong earthquakes in the region. In its middle segment, the Jinqianghe fault is an important active fault within the Tianzhu seismic gap; however, little is known about its slip behavior. To present a new horizontal displacement distribution along this fault, we used WorldView‐2 stereo pairs and unmanned aerial vehicle‐based photogrammetry to construct digital elevation models to obtain a detailed tectono‐geomorphic interpretation and geomorphic offsets. The offset marker measurements yielded 135 geomorphic displacements and 8 offset clusters. Radiocarbon dating was used to establish the regional age sequence of the geomorphic units in offset fluvial terraces at four study sites. The displacements and ages linked the offset clusters with the geomorphic unit sequence; the Holocene strike‐slip rate of the Jinqianghe fault was estimated to 4.8–5.6 mm/a at ∼4–12 ka and 2.9–4.7 mm/a from ∼4 ka. Three recent earthquakes (with a recurrence interval of ∼1000 years) represent an active seismic period, revealing the potential seismic hazard along this fault because it has not ruptured in the last 1500 years.
Geological and Geochemical Characteristics of the Zhiluo Formation in the Bayinqinggeli Uranium Deposit, Northern Ordos Basin: Significance for Uranium Mineralization
Authors: CAI Yuqi , HAN Meizhi , ZHANG Chuang , YI Chao , LI Xiaocui , ZHANG Yan , WANG Gui , LI Huaming
Published: November 2021

The Bayinqinggeli deposit in the northern Ordos Basin, northwestern of China, is a recently discovered sandstone‐type uranium deposit. The uranium (U) orebodies are generally hosted in the lower member of the Jurassic Zhiluo Formation (Fm.), and are primarily tabular or irregular in shape. In the study area, 23 sandstone samples were collected from the Zhiluo Fm. and analyzed for major, trace, and rare earth elements (REEs). The geochemical characteristics of these sandstones are used to evaluate the factors controlling U mineralization. The source rocks of the Zhiluo Fm. sandstones are mainly volcanic and felsic magmatic rocks formed in continental arc and active continental‐marginal arc environments, and they provided the material required for the mineralization. The index of compositional variability ranges from 1.02 to 3.29 (average1.38), indicating that the Zhiluo Fm. sandstones are immature and composed of first‐cycle sediments. The corrected chemical index of alteration averages 56, suggesting that the source rocks underwent weak chemical weathering. The ore host rocks are loose, providing favorable conditions for epigenetic oxidation and U precipitation and enrichment. Ferrous iron in minerals such as chlorite, biotite, ilmenite, and pyrite might have played a role either in adsorbing or reducing the uranium.
Maritime Labour, Circulations of Struggle, and Constructions of Transnational Subaltern Agency: The Spatial Politics of the 1939 Indian Seafarers’ Strikes
Authors: Featherstone David
Published: November 2021

This paper explores the relations between maritime labour, the circulation of struggles between different sites, and constructions of transnational subaltern agency. It does this through engaging with the interconnected strikes of Indian merchant seafarers in ports and ships across the British Empire in the Autumn of 1939. These strikes broke out after the outbreak of the Second World War and were in part mobilised against the racialised inequalities which structured maritime labour. The paper foregrounds the relations between practices of blockading ships in ports through refusing to crew them and the circulation of the strikes between ships. I argue that this combination of spatial tactics shaped transnational forms of networked subaltern agency (Balachandran 2012,Globalizing Labour? Indian Seafarers and World Shipping, c. 1870−1945). To engage with the dynamics of subaltern agency through the strikes the paper explores the relations between trajectories of organising, the circulation of demands, and the formation of solidarities.
Laparoscopic hemostasis for abdominal brunt massive hemorrhage due to endometriosis
Authors: Seki Shiori , Ito Kyoji , Takemura Nobuyuki , Oikawa Ryo , Koutake Hikaru , Mihara Fuminori , Yagi Junko , Nakanishi Misao , Tomio Kensuke , Oishi Hajime , Kokudo Norihiro
Published: November 2021

In the gynecological literature, a limited number of studies have reported intraperitoneal bleeding due to abdominal blunt trauma. In this report, we describe a rare case of massive intraabdominal hemorrhage from the uterine artery triggered by a fall injury without apparent abdominal bruising in the presence of severe endometriosis and a uterine fibroid. A 28‐year‐old woman who fell from a railway platform was transported to an emergency hospital. Although she did not sustain abdominal bruising and initially had no abdominal symptoms, she complained of gradually worsening abdominal pain. Abdominal CT identified intraabdominal massive hematoma, and emergency exploratory laparoscopy revealed active bleeding from the right uterine artery eroded by endometriosis, which was treated with laparoscopic electrocoagulation. The cause of the intraabdominal bleeding was associated with avulsion of the endometriosis adhesion between the right perimetrium and the right uterine artery due to inertial forces of the uterus during the fall injury. A uterine fibroid discovered during laparoscopy was suspected to strengthen the inertial forces of the uterus. In the case of hemoperitoneum after trauma, gynecological sources of bleeding must be kept in mind, especially for patients with a known history of fibroids or endometriosis.
Eight‐month repellency and efficacy of an imidacloprid/flumethrin (Seresto®) collar against the eastern paralysis tick (Ixodes holocyclus) on cats
Authors: Smith VM , de Burgh SG , Jackson CM , Chambers MA , Page PC
Published: November 2021

Objective

The objective of this study was to determine the repellency and efficacy of a 10% imidacloprid/4.5% flumethrin (Seresto®, Elanco) collar over an 8‐month period against the eastern paralysis tick (Ixodes holocyclus) on cats.

Methods

Two non‐blinded, open gender, randomised, placebo‐controlled pen studies were conducted, with 26 cats enrolled in each study. Prior to inclusion, cats were immunised with I. holocyclus holocyclotoxin. Cats were treated on Day 0 with either an imidacloprid/flumethrin or placebo collar. Tick infestations with 20 unfed adult female eastern paralysis ticks commenced on Day 7, and were repeated monthly for 8 months. Repellency was determined by comparing the mean number of attached ticks on imidacloprid/flumethrin treated cats, to placebo collar treated cats at 6 and 24 h post infestation. Efficacy was determined by comparing the mean number of live ticks on imidacloprid/flumethrin collar treated cats to placebo collar treated cats at 72 h post infestation.

Results

Efficacy was 100% (P < 0.001) at 72 h, and repellency was greater than 96% (P < 0.001) at 24 h for every tick challenge in each of the two studies, from Day 7 to the final infestation at 8 months for imidacloprid/flumethrin collar treated cats.

Conclusions

In two pen studies, an imidacloprid/flumethrin collar controlled and repelled the eastern paralysis tick (I. holocyclus) on cats for 8‐months. The marked repellency effect in addition to controlling tick paralysis would be beneficial in preventing tick bites and their sequelae.
A new perspective on technology‐driven creativity enhancement in the Fourth Industrial Revolution
Authors: Pedota Mattia , Piscitello Lucia
Published: November 2021

Technology is generally assumed to complement workers performing creative tasks by enhancing their ability to gather, store, share and transform knowledge. We advance an alternative view by conceptualizing how technology complements workers also by extending the domain, namely the set of symbolic and material elements underlying a given creative task. We elucidate the ways in which a domain extension complements workers' individual components of creativity, namely, domain‐relevant skills, creativity‐relevant processes and task motivation. Furthermore, we underline the importance of renewing heuristics to reap the creativity‐enhancing potential of the domain extension, as well as the role of the organizational context in this regard. Finally, we provide an illustrative example of our framework, referring to the adoption of additive manufacturing in Luxottica.
The Innovation System Roadmap: A novel approach to instil futures‐oriented reasoning in strategic decision making
Authors: Vettorello Mattia , Eisenbart Boris , Ranscombe Charlie
Published: November 2021

Society is in constant flux and increasing in complexity, challenging organizations to approach innovation in a more proactive manner. This entails anticipating, rather than reacting to what could be next by preparing for a variety of possible futures. Specifically, it means exploring the future value of an idea rather than analysing it as is. In the context of the fuzzy front end of a new product development, scholars highlight the efficacy of using anticipatory systems and the underlying futures‐oriented reasoning to make more accurate decision making (i.e., futures thinking, abductive reasoning and contingency mapping). Yethowto systematically stimulate such reasoning in practice is still understudied. The paper presents findings from semistructured interviews with expert innovation managers, which show that futures thinking approaches do feature in strategic decision making on innovation ideas. Yet they are limited in their use and in most cases outweighed by more classical, deductive reasoning patterns. The paper proposes the Innovation System Roadmap (ISR) for innovation managers making strategic decisions on early‐stage ideas. It leads users to employ the cognitive processes underlying anticipatory systems. The Innovation System Roadmap stimulates innovation managers to hypothesize the future value of a given innovation idea and how it may (not) be turned into a commercial success following further development. We contend that the Innovation System Roadmap supports innovation managers for sound decision making in early‐stage innovation under extreme uncertainties.
Food reward induction of rhythmic clock gene expression in the prefrontal cortex of rats is accompanied by changes in miR‐34a‐5p expression
Authors: Herichová Iveta , Tesáková Barbora , Kršková Lucia , Olexová Lucia
Published: November 2021

The current study is focused on mechanisms by which the peripheral circadian oscillator in the prefrontal cortex (PFC) participates in food reward‐induced activity. The experimental group of male Wistar rats was trained to receive a food reward with a low hedonic and caloric value. Afterwards, animals were exposed to a 5 h phase advance. Experimental animals could access a small food reward as they had been accustomed to, while control rats were exposed to the same phase shift without access to a food reward. When synchronisation to a new light:dark cycle was accompanied by intake of food reward, animals exerted more exact phase shift compared to the controls. In rats with access to a food reward, a rhythm in dopamine receptors types 1 and 2 in the PFC was detected. Rhythmic clock gene expression was induced in the PFC of rats when a food reward was provided together with a phase shift. The per2 and clock genes are predicted targets of miR‐34a‐5p. The precursor form of miR‐34a‐5p (pre‐miR‐34a‐5p) showed a daily rhythm in expression in the PFC of the control and experimental groups. On the other hand, the mature form of miR‐34a‐5p exerted an inverted rhythm compared to pre‐miR‐34a‐5p and negative correlation with per and clock genes expression only in the PFC of rewarded rats. A difference in the pattern of mature and pre‐miR‐34a‐5p values was not related to expression of enzymes drosha, dicer and dgcr8. A role of the clock genes and miR‐34a‐5p in reward‐facilitated synchronisation has been hypothesised.
Critical Reflection and the Limits of Parental Authority
Authors: Dietrich Frank
Published: November 2021

In modern pluralist societies, the meaning and value of individual autonomy is highly contested. Typically, some religious groups deny the ideal of leading a self‐directed life and regard strict obedience to God's commands as the primary goal of child education. This article pursues the question of whether a liberal state may legitimately interfere with parental authority in order to protect the development of a child's inner capacity for autonomy. It is argued that the ability to critically re‐evaluate one's life plan is valuable for the offspring of secular and pious parents alike. Therefore, restrictions on parental rights can be justified within a liberal theoretical framework that is neutral between autonomous and heteronomous conceptions of the good. However, religious parents need not be prepared to call their most important tenets into question; they may foster their children's capacity for critical reflection in other ways. Since the vast majority of religious families meet this requirement, state interventions are rarely warranted.
Bortezomib alleviates antibody‐mediated rejection in kidney transplantation by facilitating Atg5 expression
Authors: Cheng Hong , Xu Bin , Zhang Lijie , Wang Yi , Chen Ming , Chen Shuqiu
Published: November 2021

Antibody‐mediated rejection (AMR) is one of the most dominant mechanisms responsible for the loss of kidney grafts. Previous researches have shown that donor‐specific antibodies (DSAs) are the major mediators of AMR. In order to prolong the survival time of grafts, it is vital to reduce the incidence of AMR and inhibit the generation of DSAs. We established an animal model of AMR by performing kidney transplantation in pre‐sensitized rats. Then, we investigated the effect of bortezomib (BTZ) on AMR. We found that BTZ could reduce the serum level of DSAs and alleviate post‐transplantation inflammation in peritubular capillaries (PTCs) and glomeruli, which was demonstrated by the reduction of C4d and IgG deposition in PTCs, and the reduced number of B cell and plasma cell in peripheral blood and the transplanted kidney (p < 0.05). Our results also suggested that BTZ increased the number of regulatory T cell (Treg) and significantly reduced the proportion of T helper (Th17) cell (p < 0.05). Besides, BTZ induced the significant upregulation of anti‐inflammatory cytokines but downregulated pro‐inflammatory cytokines (p < 0.05). After dealing with Atg5 siRNA‐lentivirus, the effect of BTZ alleviating AMR was reversed and Th17/Treg proportions were also significantly modulated. Collectively, these findings show that BTZ slows down the process of AMR and Atg5 may be the key mechanism. Furthermore, Atg5 silencing results may be demonstrated that Atg5 alleviated AMR by modulating the ratio of Th17/Treg.
Stress‐induced phosphoprotein 1 restrains spinal cord ischaemia‐reperfusion injury by modulating NF‐κB signalling
Authors: Jin Hongdou , Ge Xin , Huan Zhirong , Yao Hao , Xu Ce , Cai Jimin
Published: November 2021

Spinal cord injury (SCI), a major cause of disability, causes high global disease and economic burdens. Stress‐induced phosphoprotein 1 (STIP1) has been identified to be involved in spinal cord ischaemia‐reperfusion injury (SCII); however, the effect of STIP1 on SCII remains unclear until now. This study aimed to examine the role of STIP1 in SCII and unravel the possible mechanisms. Western blotting and immunohistochemical staining showed that STIP1 expression rapidly increased and then decreased in rat spinal cord following SCII treatment. Neurological function scoring, HE staining, immunohistochemical staining and Western blotting revealed that STIP1 overexpression alleviated SCII‐induced motor dysfunction of hind limbs, neuronal loss and inflammation in spinal cord, and inhibited activity of nuclear factor kappa B (NF‐κB) signalling in rats. Immunoprecipitation identified that STIP1 was co‐located with Iba‐1. In addition, STIP1 was found to ameliorate oxygen and glucose deprivation (OGD)‐induced inflammation and activation of NF‐κB signalling in mouse microglia BV2 cells, and STIP1 resulted in decrease of heat shock protein family A member 8 (HSPA8), increase of IκBβ expression and reduced binding of IκBβ to HSPA8 in BV2 cells. The results of the present study demonstrate that STIP1 alleviates ischaemia/reperfusion‐induced neuronal injury and inflammation in rat spinal cord and mouse microglial cells by deactivating NF‐κB signalling. These findings may provide novel insights for the clinical diagnosis and treatment of SCI.
Tilling another's land: Migrant farming under rural industrialization and urbanization in China
Authors: Kan Karita , Chen Xi
Published: November 2021

Studies of labour migration in China usually focus on rural residents seeking wage employment in the urban industrial or service sector. This article provides an account of migrant farmers who have moved from the impoverished countryside to peri‐urban villages in more developed areas to engage in substitute agricultural production. They took over fields abandoned by local villagers and lived and worked among them as tenants. This article situates the analysis of migrant farming within the changing regimes of rural accumulation in post‐socialist China. It shows how migrant farming subsidized rural industrialization by providing low‐cost substitute labour, which facilitated the incorporation of local villagers into the industrial workforce as semi‐proletarianized workers. Into the 2000s, the transition towards land‐based accumulation incorporated local villagers into proprietorship while dispossessing migrant farmers. The amplification of inequalities reveals how the shifting regimes of accumulation constitute an important source of differentiation in Chinese villages today.