bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of MerTK in promoting cell migration is enhanced by the oncogenic Ras/IL‐33 signaling axis
Authors: Ohta Satoshi , Tago Kenji , Kuchimaru Takahiro , Funakoshi‐Tago Megumi , Horie Hisanaga , Aoki‐Ohmura Chihiro , Matsugi Jitsuhiro , Yanagisawa Ken
Published: November 2021

Ras genes are frequently mutated in many cancer types; however, there are currently no conclusively effective anticancer drugs against Ras‐induced cancer. Therefore, the downstream effectors of Ras signaling need to be identified for the development of promising novel therapeutic approaches. We previously reported that oncogenic Ras induced the expression of NF‐HEV/IL‐33, a member of the interleukin‐1 family, and showed that intracellular IL‐33 was required for oncogenic Ras‐induced cellular transformation. In the present study, we demonstrated that the c‐Mer proto‐oncogene tyrosine kinase (MerTK), a receptor tyrosine kinase, played essential roles in oncogenic Ras/IL‐33 signaling. The expression of MerTK was enhanced in transformed NIH‐3T3 cells by the expression of oncogenic Ras, H‐Ras (G12V), in an IL‐33‐dependent manner. In human colorectal cancer tissues, MerTK expression also correlated with IL‐33 expression. The knockdown of IL‐33 or MerTK effectively attenuated the migration of NIH‐3T3 cells transformed by H‐Ras (G12V) and A549, LoVo, and HCT116 cells harboring an oncogenic K‐Ras mutation. Furthermore, the suppression of Ras‐induced cell migration by the knockdown of IL‐33 was rescued by the enforced expression of MerTK. The present results also revealed that MerTK was effectively phosphorylated in NIH‐3T3 cells transformed by Ras (G12V). Ras signaling was essential for the tyrosine phosphorylation of MerTK, and the kinase activity of MerTK was indispensable for accelerating cell migration. Collectively, the present results reveal a novel role for MerTK in cancer malignancy, which may be utilized to develop novel therapeutic strategies that target Ras‐transformed cells.
Playing a new game—An argument for a teacher‐focused field around games and play in language education
Authors: York James , Poole Frederick J. , deHaan Jonathan W.
Published: November 2021

In this paper, we argue that current research on games in language education, predominantly framed as “digital game‐based language learning” (DGBLL), is lacking details regarding the role of teachers, or more precisely, the verbalization of the pedagogical underpinnings, scaffolds, and techniques teachers use to successfully integrate games and play in their teaching contexts. Thus, we propose a new direction of research that emphasizes the importance of teachers in game‐based language learning and argue for the necessity of an inclusive field of inquiry that is open to the diverse instantiations of games and play which exist outside the current scope of DGBLL. This new field places teachers and a deeper consideration of the connections between play and learning at the center of an approach to studying the intersection and implementation of games and language teaching. We present three “ludic language pedagogy” (LLP) studies which demonstrate what teaching with and around games looks like. Finally, we propose numerous avenues of further inquiry for teachers and researchers to advance the field of LLP.
Neighbourhood change, deprivation, and unemployment in Belfast
Authors: Lloyd Christopher D.
Published: November 2021

Much effort has been expended on measuring deprivation in neighbourhoods across the UK and elsewhere. However, there has been only a relatively limited concern with deprivation histories of areas. This paper takes as its focus Belfast in Northern Ireland and it capitalises on rich data sources on deprivation generally and unemployment specifically. The study makes use of data on multiple time points – the Census from 1971 to 2011, multiple deprivation measures for 2005, 2010, and 2017, and benefits claimant count data for 2020. The paper explores the changing geography of deprivation and unemployment, identifying areas with persistently high deprivation and unemployment across time and across measures. It is argued that trajectories are important, particularly in terms of targeting resources. The final section of the analysis uses claimant count data to assess changing unemployment rates following the outbreak of the COVID‐19 pandemic and it shows that changes in these rates are strongly related to long‐term deprivation and unemployment patterns.
Certification of Uranium Isotope Amount Ratios in a Suite of Uranium Ore Concentrate Certified Reference Materials
Authors: Zhang Ruoxi , Nadeau Kenny , Gautier Eduardo Amilcar , Babay Paola Alejandra , Ramella José Luis , Virgolici Marian , Serban Andreea Elena , Fugaru Viorel , Kimura Yoshiki , Venchiarutti Célia , Richter Stephan , Aregbe Yetunde , Varga Zsolt , Wallenius Maria , Mayer Klaus , Seo Hana , Choi Jung Youn , Tobi Csaba , Fayek Mostafa , Sharpe Ryan , Samperton Kyle M. , Genetti Victoria D. , Lindvall Rachel E. , Inglis Jeremy D. , Denton Joanna S. , Reinhard Andrew A. , Francisco Barbara , Zhao Xiaolei , Kieser William , He Juan , Gao Ying , Meija Juris , El‐Jaby Ali , Yang Lu , Mester Zoltan
Published: November 2021

In this study, data from thirteen laboratories from around the world are presented for a successful certification of uranium isotope ratios in uranium ore concentrate (UOC) certified reference materials from the National Research Council Canada. Different mass spectrometric measurement principles (including SF‐ICP‐MS, quadruple ICP‐MS, TIMS, MC‐ICP‐MS, SIMS and AMS) and measurement procedures were employed. In general, data from all sources exhibit good consistency with TIMS and MC‐ICP‐MS showing superior performance. The three candidate UOC CRMs (UCLO‐1, UCHI‐1 and UPER‐1) have natural uranium isotope ratios with certified values of 0.5304(7) × 10−4, 0.5475(2) × 10−4 and 0.5361(4) × 10−4 for n(234U)/n(238U) and 0.007 2563(13), 0.007 2563(10) and 0.007 2542(11) for n(235U)/n(238U), respectively, with expanded uncertainty (k = 2) applicable to the last digit of the value given in the parentheses. Information values for n(236U)/n(238U) in these three CRMs, measured by AMS, are also provided: 10 × 10−12, 200 × 10−12 and 22 × 10−12. The uncertainties of the proposed certified values of uranium isotope ratios in UOC CRMs are superior to available reference materials, and the values of n(234U)/n(238U) and n(236U)/n(238U) show significant variation among the three CRMs.
A comparison of three major instruments used for the assessment of university student experience: Toward a comprehensive and distributed approach
Authors: Zeng Lily Min , Fryer Luke K. , Zhao Yue
Published: November 2021

Higher education's rapid expansion is paired with growing social expectations of its benefits and concern on its teaching quality. In response to these, institutional/national surveys based on an array of theories are widely used in universities for quality assurance, enhancement, and benchmarking. This paper reviews three major types of instruments used for such purposes, including two distinct schools of theory that have guided the development of such assessment in the United States, Australia and the United Kingdom and then spread to the other parts of the world. The theories shaping the development of the two instruments, the dimensions assessed, and the challenges and criticisms involved when using such instruments for quality assurance are each discussed. This review concludes with a call for comparisons of different lines of research in this area, discussions on student learning experience that include more diverse characterizations of student experience across different educational contexts, development of tools to enable distributed leadership among teachers, and encouragement of students as partners for quality enhancement in higher education.
Additive manufacturing of novel 3D ceramic electrodes for high‐power‐density batteries
Authors: Almansour Amjad S. , Gorven Alastair J. , Singh Mrityunjay
Published: November 2021

The development of batteries with high‐specific power and energy densities will enable more efficient implementation of all‐electric aircraft and urban air mobility technologies. Additive manufacturing technologies can be leveraged to produce engineered three‐dimensional electrode structures with increased electrolyte/electrode interfacial area and high density, yielding increased power and energy densities. In this work, a novel engineered three‐dimensional interdigitated LiFePO4 cathode structure was designed and manufactured using direct‐write additive manufacturing technology, which allowed for the deposition of highly solid‐loaded inks with excellent dimensional accuracy. Ink rheology was adjusted to optimize material characteristics of the final electrodes, including the addition of carbon nanoparticles to increase the final electrode conductivity. Printed cathodes were then sintered and characterized. The sintered electrodes possessed greater structural stability and a surface area approximately 190% greater than similarly produced devices reported in the literature. Finally, the characterization of the manufactured electrodes showed uniform dispersion of conductive carbon nanopowder throughout the microstructure, which could increase the final conductivity of the electrodes.
The effect of diphenyliodonium iodide treatment on bisdemethoxycurcumin accumulation in fresh‐cut yam
Authors: Guo Shuang , Ma Yue , Liang Hao , Zhao Xiaoyan , Wang Dan
Published: November 2021

Yellowing is a main discoloration in fresh‐cut yam, which reduces consumer acceptance and, hence, the commodity value. Bisdemethoxycurcumin has been demonstrated to play important roles in fresh‐cut yam yellowing. Considering the pharmacological properties and application in fruits and vegetables of diphenyliodonium iodide (DPI), the effects and mechanism of DPI treatment on bisdemethoxycurcumin accumulation in fresh‐cut yam were analysed. The results showed that total bisdemethoxycurcumin in fresh‐cut yam treated with DPI was markedly inhibited due to the significantly weakened phenylpropanoid pathway and bisdemethoxycurcumin biosynthesis. DPI was found to suppress the activities of major enzymes (phenylalanine ammonia lyase, PAL, cinnamate‐4 hydroxylase, C4H; 4‐coumarate coenzyme A ligase, 4CL), limit the levels of PAL, C4H and 4CL transcription and lower the contents of related metabolites in fresh‐cut yam. Moreover, treatment with DPI inhibitor restrained the downstream transcription level of curcumin synthase (CURS), which had a significant impact on bisdemethoxycurcumin synthesis. Thus, our results confirmed that DPI was essential for inhibiting bisdemethoxycurcumin accumulation in fresh‐cut yam through suppressed phenylpropanoid pathway and bisdemethoxycurcumin biosynthesis.
Effect of heat and relative humidity treatment on γ‐aminobutyric acid accumulation, other micronutrients contents, antioxidant activities and physicochemical properties of mung bean (Vigna radiata L.)
Authors: Ma Yuling , Tong Litao , Wang Shanshan , Liu Tingyu , Wang Lili , Liu Liya , Zhou Xianrong , Zhou Sumei , Blecker Christophe
Published: November 2021

A novel approach to heat and relative humidity (HRH, 65‐75 °C, 98% RH) treatment was used to enhance γ‐aminobutyric acid (GABA) of mung bean with a low moisture (12‐20%) within several hours (4‐6 h). Meanwhile, the changes in micronutrients, antioxidant activities and physicochemical properties were also evaluated. Results showed that the GABA content was significantly accumulated, increasing from 1.73 to 109.78 mg 100 g−1 dry weight (DW) under the conditions of 16.72% moisture, 68.97 °C, 98% RH for 5.34 h. Meanwhile, the amino acids, including aromatic (tyrosine and phenylalanine), sulphur‐containing (methionine and cystine) and branched‐chain amino acids (leucine, isoleucine and valine), were significantly increased (P < 0.05). Although HRH treatment decreased the total anthocyanin content of mung bean, the total phenolic, vitexin and isovitexin contents, and antioxidant activities were significantly increased (P < 0.05). Furthermore, HRH treatment caused the wrinkled structure of mung bean coat, increased the paste viscosity of mung bean flour and decreased the time of complete gelatinisation of starch in mung bean by one third during cooking. These results suggested that HRH treatment could effectively elevate the above functional components, especially GABA, improve the antioxidant activities, pasting and cooking properties of mung bean.
Freedom of association and collective bargaining in the platform economy: A human rights‐based approach and an ever‐increasing mobilization of workers
Authors: STYLOGIANNIS Charalampos
Published: November 2021

This paper examines the exercise of the rights to freedom of association and collective bargaining by platform workers. It focuses on several significant developments involving the collective organization of platform workers worldwide, and considers the rights to freedom of association and collective bargaining as human rights. It contends that the shifting context of work has led to changes in modern workplaces, which, in turn, have generated a novel interest in the adoption of a human rights‐based approach towards labour protection. This approach considers that all workers are entitled to rights, such as the right to collective bargaining, which derive from international human rights instruments.
Development of type 1 diabetes in a patient treated with anti‐interleukin‐6 receptor antibody for rheumatoid arthritis
Authors: Kawasaki Eiji , Fukuyama Takahiro , Uchida Aira , Sagara Yoko , Nakano Yuko , Tamai Hidekazu , Tojikubo Masayuki , Hiromatsu Yuji , Koga Nobuhiko
Published: November 2021

Interleukin‐6 is a pleiotropic cytokine that plays a pathogenic role in type 1 diabetes. Therefore, anti‐interleukin‐6 receptor antibody, tocilizumab, used for the treatment of rheumatoid arthritis, is considered a candidate for immune intervention in type 1 diabetes. Here, we report the case of a 73‐year‐old woman (HLA‐DR9‐DQ3 homozygote) with well‐controlled rheumatoid arthritis who developed type 1 diabetes while receiving tocilizumab treatment. At 57 years‐of‐age, the patient was diagnosed with rheumatoid arthritis, for which she underwent tocilizumab therapy that enabled complete suppression of her joint inflammation. A total of 17 months after starting tocilizumab therapy, she noticed polydipsia, polyuria, general fatigue and weight reduction (−2 kg/month), and was diagnosed with type 1 diabetes with diabetic ketoacidosis based on an arterial pH of 7.26, serum ketone body of 7,437 μmol/L, blood glucose level of 925 mg/dL, glycated hemoglobin of 13.2% and the presence of anti‐islet autoantibodies. This case report shows valuable insight regarding the effect of anti‐interleukin‐6 receptor antibody therapy on type 1 diabetes prevention.
Usefulness of subclassification of adult diabetes mellitus among inpatients in Japan
Authors: Saito Kohei , Inoue Tatsuhide , Ariyasu Hiroyuki , Shimada Toshio , Itoh Hiroshi , Tanaka Issei , Terao Chikashi
Published: November 2021

Aims/Introduction

We aimed to replicate a new diabetes subclassification based on objective clinical information at admission in a diabetes educational inpatient program. We also assessed the educational outcomes for each cluster.

Methods

We included diabetes patients who participated in the educational inpatient program during 2009–2020 and had sufficient clinical information for the cluster analysis. We applied a data‐driven clustering method proposed in a previous study and further evaluated the clinical characteristics of each cluster. We investigated the association between the clusters and changes in hemoglobin A1c level from the start of the education program. We also assessed the risk of re‐admission for the educational program.

Results

We divided a total of 651 patients into five clusters. Their clinical characteristics followed the same pattern as in previous studies. The intercluster ranking of the cluster center coordinates showed strong correlation coefficients with those of the previous studies (mean ρ = 0.88). Patients classified as severe insulin‐resistant diabetes (cluster 3) showed a more pronounced progression of renal dysfunction than patients classified as the other clusters. The patients classified as severe insulin‐deficient diabetes (cluster 2) had the highest rate of reduction in hemoglobin A1c level from the start of the program (P < 0.01) and a tendency toward a lower risk of re‐admission for the education program (hazard ratio 0.47, P = 0.09).

Conclusion

We successfully replicated the diabetes subclassification using objective clinical information at admission for the education program. In addition, we showed that severe insulin‐deficient diabetes patients tended to have better educational outcomes than patients classified as the other clusters.
Atopic dermatitis: disease characteristics and comorbidities in smoking and non‐smoking patients from the TREATgermany registry
Authors: Pilz A.C. , Schielein M.C. , Schuster B. , Heinrich L. , Haufe E. , Abraham S. , Heratizadeh A. , Harder I. , Kleinheinz A. , Wollenberg A. , Wiemers F. , Weisshaar E. , Augustin M. , von Kiedrowski R. , Pawlak M. , Schäkel K. , Wildberger J. , Hilgers M. , Werfel T. , Weidinger S. , Schmitt J. , Biedermann T. , Zink A. ,   and the TREATgermany Study Group
Published: November 2021

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke.

Objectives

In this study, AD characteristics and its atopic comorbidities are compared in smoking and non‐smoking AD patients.

Methods

TREATgermany is a non‐interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non‐smokers.

Results

Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non‐smokers, however, lesions’ intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non‐smoking patients. Smokers reported a lower number of weeks with well‐controlled AD and more severe pruritus than non‐smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well‐controlled AD and the greater pruritus remained different in smokers compared to non‐smokers. In addition, smoking patients with adult‐onset AD showed a 2.5 times higher chance of involvement of the feet.

Conclusions

German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult‐onset AD.
Impact of oral abrocitinib on signs, symptoms and quality of life among adolescents with moderate‐to‐severe atopic dermatitis: an analysis of patient‐reported outcomes
Authors: Cork M.J. , McMichael A. , Teng J. , Valdez H. , Rojo R. , Chan G. , Zhang F. , Myers D.E. , DiBonaventura M.
Published: November 2021

Background

A significant improvement in clinical signs was demonstrated with abrocitinib relative to placebo in adolescents with moderate‐to‐severe atopic dermatitis (AD) in three phase 3, randomized, double‐blinded, placebo‐controlled studies (JADE TEEN [ClinicalTrials.gov, NCT03796676], JADE MONO‐1 [NCT03349060] and JADE MONO‐2 [NCT03575871]).

Objectives

To evaluate the impact of abrocitinib on patient‐reported signs/symptoms, including sleep loss and quality of life among adolescents with moderate‐to‐severe AD.

Methods

JADE TEEN, JADE MONO‐1 and JADE MONO‐2 were conducted in the Asia‐Pacific region, Europe and North America and included patients aged 12–17 years with moderate‐to‐severe AD and inadequate response to ≥ 4 consecutive weeks of topical medication or treatment with systemic therapy for AD. Patients were randomly assigned (1 : 1 : 1, JADE TEEN; 2 : 2 : 1, JADE MONO‐1/‐2) to receive once‐daily oral abrocitinib (200 or 100 mg) or placebo for 12 weeks in combination with topical therapy (JADE TEEN) or as monotherapy (JADE MONO‐1/‐2). Data from adolescent patients in JADE MONO‐1/‐2 were pooled for these analyses.

Results

At week 12, more adolescents treated with abrocitinib (200 or 100 mg) vs. placebo achieved a ≥ 4‐point improvement from baseline in the Patient‐Oriented Eczema Measure in JADE TEEN (83.9% and 77.0% vs. 60.2%) and JADE MONO‐1/‐2 (83.0% and 69.4% vs. 43.5%) and a ≥ 6‐point improvement from baseline in the Children’s Dermatology Life Quality Index in JADE TEEN (73.8% and 67.5% vs. 56.5%) and JADE MONO‐1/‐2 (70.0% and 57.1% vs. 19.0%). Significant improvements in SCORing Atopic Dermatitis Visual Analog Scale for sleep loss scores were demonstrated with abrocitinib vs. placebo at weeks 2‐12 in JADE TEEN and JADE MONO‐1/‐2.

Conclusions

Patient‐reported signs/symptoms, including reduction of sleep loss and quality of life, were substantially improved with abrocitinib monotherapy or combination therapy relative to placebo in adolescents with moderate‐to‐severe AD.
Influence of an elevated CO2level on life history parameters and hormone pathway or vitellogenin metabolism of the brown planthopper
Authors: Wang Yanhui , Liu Hui , Wang Xiaohui , Liu Xiaowei , Chen Fajun
Published: November 2021

The growth, development and reproduction of herbivorous insects could be altered due to changes in quality and quantity of their host plants under elevated CO2. The brown planthopper,Nilaparvata lugens, is one of the most serious and destructive economic pests in rice growing areas in Asia. In this study, we investigated the effect of elevated CO2on the growth, development and reproduction ofN. lugensand, in particular, on the hormonal regulation of the transcription factors inN. lugens. The results indicated that compared with ambient CO2, elevated CO2significantly shortened the duration of egg and nymph, longevity of female adults and total adults, and significantly decreased the weight of adults; besides, elevated CO2significantly improved the fecundity of female adults, egg hatching rata and the transcription levels ofVg. The relative expression levels ofJHMAT‐andFAMeT‐regulated synthesis of JH were first down‐regulated and then up‐regulated with the development of the 5th instar nymph ofN. lugensunder elevated CO2. In addition, the relative expression level ofcyp314a1played an important role in synthesis of ecdysone was up‐regulated in the 5th instar nymph ofN. lugensunder elevated CO2. We have demonstrated that elevated CO2could accelerate the development and improve the reproduction ofN. lugens, which is related to the transcription levels of JH, MH and Vg.
An Arabidopsis vasculature distributed metal tolerance protein facilitates xylem magnesium diffusion to shoots under high‐magnesium environments
Authors: Ge Haiman , Wang Yuan , Chen Jinlin , Zhang Bin , Chen Rui , Lan Wenzhi , Luan Sheng , Yang Lei
Published: November 2021

Magnesium (Mg2+) is an essential metal for plant growth; however, its over‐accumulation in cells can be cytotoxic. The metal tolerance protein family (MTP) belongs to an ubiquitous family of cation diffusion facilitator (CDF) proteins that export divalent metal cations for metal homeostasis and tolerance in all organisms. We describe here the identification of MTP10 to be critical for xylem Mg homeostasis in Arabidopsis under high Mg2+ conditions. The Arabidopsis plant contains 12 MTP genes, and only knockout of MTP10 decreased the tolerance of high‐Mg stress. The functional complementation assays in a Mg2+ ‐uptake‐deficient bacterial strain MM281 confirmed that MTP10 conducted Mg2+ transport. MTP10 is localized to the plasma membrane of parenchyma cells around the xylem. Reciprocal grafting analysis further demonstrated that MTP10 functions in the shoot to determine the shoot growth phenotypes under high Mg2+ conditions. Moreover, compared to the wild type, the mtp10 mutant accumulated more Mg2+ in xylem sap under high‐Mg stress. This study reveals that MTP10 facilitates Mg2+ diffusion from the xylem to shoots and thus determines Mg homeostasis in shoot vascular tissues during high‐Mg stress.
The HDL mimetic CER‐001 remodels plasma lipoproteins and reduces kidney lipid deposits in inherited lecithin:cholesterol acyltransferase deficiency
Authors: Pavanello Chiara , Turri Marta , Strazzella Arianna , Tulissi Patrizia , Pizzolitto Stefano , De Maglio Giovanna , Nappi Riccardo , Calabresi Laura , Boscutti Giuliano
Published: November 2021

Background

Kidney failure is the major cause of morbidity and mortality in familial lecithin:cholesterol acyltransferase deficiency (FLD), a rare inherited lipid disorder with no cure. Lipoprotein X (LpX), an abnormal lipoprotein, is primarily accountable for nephrotoxicity.

Methods

CER‐001 was tested in an FLD patient with dramatic kidney disease for 12 weeks.

Results

Infusions of CER‐001 normalized the lipoprotein profile, with a disappearance of the abnormal LpX in favour of normal‐sized LDL. The worsening of kidney function was slowed by the treatment, and kidney biopsy showed a slight reduction of lipid deposits and a stabilization of the disease. In vitro experiments demonstrate that CER‐001 progressively reverts lipid accumulation in podocytes by a dual effect: remodelling plasma lipoproteins and removing LpX‐induced lipid deposit.

Conclusion

This study demonstrates that CER‐001 may represent a therapeutic option in FLD patients. It also has the potential to be beneficial in other renal diseases characterized by kidney lipid deposits.
Cercospora species cause pink spot disease on guava fruit in Brazil
Authors: Shirado Evelyn N. , Marques João Paulo Rodrigues , Alves Renan Fernandes , Appezzato‐da‐Glória Beatriz , Navarro Bárbara Ludwig , Fischer Ivan Herman , Spósito Marcel Bellato
Published: November 2021

Guava producers in Brazil have reported the occurrence of small, pink spot lesions on the surface of fruits in orchards. Symptomatic fruits were harvested from commercial guava orchards, and 18 monosporic isolates were obtained. All tested isolates were pathogenic to guava fruit and showed colony and conidial characteristics indicative of cercosporoid fungi. Phylogenetic analysis of the concatenated gene sequences showed that all isolates belonged to the genus Cercospora and clustered into four haplotypes. Conidia released 3–5 germ tubes, and penetration occurred through the stomata. All isolates produced cercosporin. Histopathological analyses showed that hyphal growth occurred intercellularly and that there was a collapse of epidermal and subepidermal cells in the injured areas. In addition, the oil cavities in the lesioned tissue had large numbers of lipid droplets compared with the nonlesioned tissue. This is the first report of Cercospora spp. as the causal agent of pink spot disease of guava fruit in Brazil.
Enhancing geographical indications protection in India for community relevance
Authors: Datta Sayantani , Manchikanti Padmavati , Bhattacharya Niharika S.
Published: November 2021

Geographical indications (GI) rights are unique as they have a regio‐cultural basis and involve the knowledge and skill of communities. The enactment of the Indian GI Act 1999 was aimed to improve the economic status of the communities and key products for export by registration of GI. Analysis of the inspection body particular, institutional mechanism, and registration process revealed the need for elaboration of GI protection mechanism. Of particular significance is the need to protect the reputation of GIs, strengthen the local registration mechanism, and identify a mechanism for monitoring and conservation of GI. Analysis of food GI such as Bardhaman Sitabhog and Mihidana provide insights on the need for an enhanced protection mechanism to be provided under the GI Act and the rules which have a significant bearing on the post GI sustenance.
Institutional incongruence and unauthorized copying in Poland
Authors: Czetwertyński Sławomir
Published: November 2021

The aim of this article was to find out how the cognitive dissonance resulting from the occurrence of institutional incongruence in the context of copying information goods in online society is reduced. The implementation of this goal required conceptualization work and empirical research. The conceptual part was based on the theory of cognitive dissonance by Festinger as well as works on the concept of institutional congruence. The essence of the conceptualization work was the formulation of the concept of institutional incongruence, which leads to a cognitive dissonance that requires reduction. The empirical research conducted on Polish internet users in August 2020 was designed to allow to determine whether there is an institutional incongruence in the area of copying information goods, and how the possible dissonance resulting from such incongruence is reduced. A survey study conducted on a random sample of 1000 respondents (with a standard error of 3%). The survey took the form of a questionnaire distributed among respondents via the Badanie‐Opinii.pl research panel, property of the Biostat Research and Development Centre. Empirical research has shown that institutional incongruence is largely imaginary (a kind of cognitive bias). In the context of dissonance reduction, there were found several forms of it: (1) the downplaying of the phenomenon of unauthorized copying, (2) an attitude that completely ignores the problem of unauthorized copying, and (3) an attitude that assumes that any form of unauthorized copying is simply “piracy.”
Circular RNA circ_GLIS2 suppresses hepatocellular carcinoma growth and metastasis
Authors: Xing Wu , Zhou Peng‐Cheng , Zhang Hao‐Ye , Chen Li‐Min , Zhou Yang‐Mei , Cui Xue‐Fei , Liu Zhen‐Guo
Published: November 2021

Background & Aims

Hepatocellular carcinoma (HCC) is one of the leading causes of tumour‐related death. Here, we investigated the molecular mechanism of HCC by studying the function of circ_GLIS2.

Methods

Human HCC specimens and cell lines were used. Sanger sequencing, actinomycin D and RNase R treatment were performed to validate circular RNA features of circ_GLIS2. qRT‐PCR, western blotting, immunostaining, and IHC were employed to examine levels of circ_GLIS2, GLIS2 mRNA, and EMT‐related markers. CCK‐8, colony formation, flow cytometry, wound healing assay, and transwell assays were performed to evaluate cancer cell proliferation, apoptosis, migration, and invasion. RIP and RNA pull‐down assay were used to validate EIF4A3/GLIS2 mRNA interaction. MSP was performed to measure the methylation status of GLIS2 promoter. Nude mouse xenograft model was used to examine tumour growth and metastasis in vivo.

Results

Circ_GLIS2 and linear GLIS2 mRNA were reduced in human HCC tissues and cells. Their low levels correlated with a poor survival rate of HCC patients. Overexpression of circ_GLIS2 and GLIS2 suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis. GLIS2 promoter region was hypermethylated in HCC cells. EIF4A3 was directly bound with GLIS2 mRNA and promoted circ_GLIS2/GLIS2 expression. Moreover, overexpression of circ_GLIS2 restrained HCC tumour growth and metastasis in vivo.

Conclusion

Circ_GLIS2 suppresses HCC growth and metastasis by inhibiting cell proliferation, migration, and invasion, but promoting cell apoptosis. These findings provide molecular insights into the mechanism of HCC and indicate that circ_GLIS2 could serve as a diagnosis marker or therapeutic target for HCC.
Datafied Pregnancies: Health Information Technologies and Reproductive Governance in Turkey
Authors: Saluk Seda
Published: November 2021

Since the early 2000s, Turkey has been going through a dynamic period of health reforms where the global push toward health statistics has converged with the state's pronatalist concerns over declining birth rates. Reproductive behaviors are now monitored via health information technologies such as centralized databases. The World Health Organization and the Turkish Ministry of Health celebrate these technologies as essential steps toward evidence‐based health care delivery. The everyday realities of these technologies, however, are more complicated, especially for nurses and their patients. Drawing on ethnographic fieldwork in state‐run health clinics in Istanbul, this article demonstrates how these data‐driven health technologies build on nurses’ gendered care labor and increase surveillance on urban poor and/or ethnoracially minoritized communities. In doing so, I argue that the datafication of reproduction operates as a particular mode of “reproductive governance” (Morgan and Roberts 2012) that reflects and reproduces existing social hierarchies and inequalities.
Serum iron indices in COVID‐19‐associated mucormycosis: A case–control study
Authors: Kumar H Mohan , Sharma Prashant , Rudramurthy Shivaprakash M. , Sehgal Inderpaul Singh , Prasad Kuruswamy Thurai , Pannu Ashok Kumar , Das Reena , Panda Naresh K. , Sharma Navneet , Chakrabarti Arunaloke , Agarwal Ritesh , Muthu Valliappan
Published: November 2021

Background

Whether dysregulated iron metabolism is associated with COVID‐19‐associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID‐19 subjects with and without mucormycosis.

Methods

We conducted a case–control study enrolling COVID‐19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron‐binding capacity [TIBC], unsaturated iron‐binding capacity and percentage transferrin saturation) between CAM cases and COVID‐19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM.

Results

We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino‐orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID‐19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 μg/dl, p = .03) and TIBC (166.6 vs. 201.6 μg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95–0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21–22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non‐survivors.

Conclusions

The CAM is associated with lower TIBC levels than COVID‐19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.
Long reads and Hi‐C sequencing illuminate the two‐compartment genome of the model arbuscular mycorrhizal symbiont Rhizophagus irregularis
Authors: Yildirir Gökalp , Sperschneider Jana , Malar C Mathu , Chen Eric C. H. , Iwasaki Wataru , Cornell Calvin , Corradi Nicolas
Published: November 2021

Chromosome folding links genome structure with gene function by generating distinct nuclear compartments and topologically associating domains. In mammals, these undergo preferential interactions and regulate gene expression. However, their role in fungal genome biology is unclear.

Here, we combine Nanopore (ONT) sequencing with chromatin conformation capture sequencing (Hi‐C) to reveal chromosome and epigenetic diversity in a group of obligate plant symbionts: the arbuscular mycorrhizal fungi (AMF).

We find that five phylogenetically distinct strains of the model AMF Rhizophagus irregularis carry 33 chromosomes with substantial within‐species variability in size, as well as in gene and repeat content. Strain‐specific Hi‐C contact maps reveal a ‘checkerboard’ pattern that underline two dominant euchromatin (A) and heterochromatin (B) compartments. Each compartment differs in the level of gene transcription, regulation of candidate effectors and methylation frequencies. The A‐compartment is more gene‐dense and contains most core genes, while the B‐compartment is more repeat‐rich and has higher rates of chromosomal rearrangement. While the B‐compartment is transcriptionally repressed, it has significantly more secreted proteins and in planta upregulated candidate effectors, suggesting a possible host‐induced change in chromosome conformation.

Overall, this study provides a fine‐scale view into the genome biology and evolution of model plant symbionts, and opens avenues to study the epigenetic mechanisms that modify chromosome folding during host–microbe interactions.
SMALL REPRODUCTIVE ORGANS, a SUPERMAN‐like transcription factor, regulates stamen and pistil growth in rice
Authors: Xu Wei , Zhu Wanwan , Yang Liu , Liang Wanqi , Li Hui , Yang Li , Chen Mingjiao , Luo Zhijing , Huang Guoqiang , Duan Lei , Dreni Ludovico , Zhang Dabing
Published: November 2021

Organ size is determined mainly by cell division and cell expansion. Several genetic factors regulating development of plant lateral organs have been characterized, but those involved in determining reproductive organ size and separation in rice (Oryza sativa) remain unknown.

We have isolated the rice gene SMALL REPRODUCTIVE ORGANS (SRO) encoding a nucleus‐localized Cys2His2 (C2H2) zinc finger protein orthologous to Arabidopsis transcription factor (TF) SUPERMAN (SUP). Combined developmental, genetic, histological and transcriptomic analyses were used to determine the function of SRO in regulating reproductive organ size.

SRO affects genes involved in cell division, cell expansion and phytohormone signalling in the rice flower. SRO is specifically expressed in the first stages of stamen filament development to regulate their correct formation and separation. In addition, SRO noncell‐autonomously regulates the size and functionality of male and female reproductive organs. The B‐class MADS‐box gene OsMADS16/SPW1 is epistatic to SRO, whereas SRO regulates reproductive organ specification and floral meristem determinacy synergistically with C‐class genes OsMADS3 and OsMADS58.

These findings provide insights into how an evolutionarily conserved TF has a pivotal role in reproductive organ development in core eudicots and monocots, through partially conserved expression, function and regulatory network.
Linking root exudation to belowground economic traits for resource acquisition
Authors: Wen Zhihui , White Philip J. , Shen Jianbo , Lambers Hans
Published: November 2021

The concept of a root economics space (RES) is increasingly adopted to explore root trait variation and belowground resource‐acquisition strategies. Much progress has been made on interactions of root morphology and mycorrhizal symbioses. However, root exudation, with a significant carbon (C) cost (c. 5–21% of total photosynthetically fixed C) to enhance resource acquisition, remains a missing link in this RES. Here, we argue that incorporating root exudation into the structure of RES is key to a holistic understanding of soil nutrient acquisition. We highlight the different functional roles of root exudates in soil phosphorus (P) and nitrogen (N) acquisition. Thereafter, we synthesize emerging evidence that illustrates how root exudation interacts with root morphology and mycorrhizal symbioses at the level of species and individual plant and argue contrasting patterns in species evolved in P‐impoverished vs N‐limited environments. Finally, we propose a new conceptual framework, integrating three groups of root functional traits to better capture the complexity of belowground resource‐acquisition strategies. Such a deeper understanding of the integrated and dynamic interactions of root morphology, root exudation, and mycorrhizal symbioses will provide valuable insights into the mechanisms underlying species coexistence and how to explore belowground interactions for sustainable managed systems.
Imatinib has minimal effects on inflammatory and osteopenic phenotypes in a murine cherubism model
Authors: Mukai Tomoyuki , Akagi Takahiko , Hiramatsu Asano Sumie , Tosa Ikue , Ono Mitsuaki , Kittaka Mizuho , Ueki Yasuyoshi , Yahagi Ayano , Iseki Masanori , Oohashi Toshitaka , Ishihara Katsuhiko , Morita Yoshitaka
Published: November 2021

Objective

Cherubism is a genetic disorder characterised by bilateral jawbone deformation. The associated jawbone lesions regress after puberty, whereas severe cases require surgical treatment. Although several drugs have been tested, fundamental treatment strategies for cherubism have not been established. The effectiveness of imatinib has recently been reported; however, its pharmaceutical mechanism remains unclear. In this study, we tested the effects of imatinib using a cherubism mouse model.

Methods

We used Sh3bp2 P416R cherubism mutant mice, which exhibit systemic organ inflammation and osteopenia. The effects of imatinib were determined using primary bone marrow‐derived macrophages. Imatinib was administered intraperitoneally to the mice, and serum tumour necrosis factor‐α (TNFα), organ inflammation and bone properties were examined.

Results

The cherubism mutant macrophages produced higher levels of TNFα in response to lipopolysaccharide compared to wild‐type macrophages, and imatinib did not significantly suppress TNFα production. Although imatinib suppressed osteoclast formation in vitro, administering it in vivo did not suppress organ inflammation and osteopenia.

Conclusion

The in vivo administration of imatinib had a minimal therapeutic impact in cherubism mutant mice. To establish better pharmaceutical interventions, it is necessary to integrate new findings from murine models with clinical data from patients with a definitive diagnosis of cherubism.
Deletion of the yqeK gene leads to the accumulation of Ap4A and reduced biofilm formation in Streptococcus mutans
Authors: Zheng Ting , Jing Meiling , Gong Tao , Yan Jiangchuan , Zeng Jumei , Li Yuqing
Published: November 2021

Diadenosine‐5′,5′′′‐P1, P4‐tetraphosphate (Ap4A) is a second messenger playing a crucial role in various life activities of bacteria. The increase of Ap4A expression is pleiotropic, resulting in an impairment in the formation of biofilm and other physiological functions in some bacteria. However, Ap4A function in Streptococcus mutans, an important pathogen related to dental caries, remains unknown. In this work, the Ap4A hydrolase, YqeK, was identified and characterized in S. mutans. Then, the effects of yqeK deletion on the growth, biofilm formation, and exopolysaccharide (EPS) quantification in S. mutans were determined by the assessment of the growth curve, crystal violet, and anthrone‐sulfuric acid, respectively, and visualized by microscopy. The results showed that the in‐frame deletion of the yqeK gene in S. mutans UA159 led to an increase in Ap4A levels, lag phase in the early growth, as well as decrease in biofilm formation and water‐insoluble exopolysaccharide production. Global gene expression profile showed that the expression of 88 genes was changed in the yqeK mutant, and among these, 42 were upregulated and 46 were downregulated when compared with the wild‐type S. mutans UA159. Upregulated genes were mainly involved in post‐translational modification, protein turnover, and chaperones, while downregulated genes were mainly involved in carbohydrate transport and metabolism. Important virulence genes related to biofilms, such as gtfB, gtfC, and gbpC, were also significantly downregulated. In conclusion, these results indicated that YqeK affected the formation of biofilms and the expression of biofilm‐related genes in S. mutans.
An evaluation of the IOLMaster 700 and its agreement with the IOLMaster v3 in children
Authors: Leighton Rebecca E , Breslin Karen MM , Saunders Kathryn J , McCullough Sara J
Published: November 2021

Purpose

To evaluate the repeatability and reproducibility of the swept‐source optical coherence tomographer Zeiss IOLMaster 700 and compare its outputs with those obtained using partial coherence interferometry (Zeiss IOLMaster v3) in a healthy, paediatric population.

Methods

This is a cross‐sectional, observational study. Examiner 1 took two sets of biometric measurements (axial length [AL], mean corneal radius of curvature [Kmean], anterior chamber depth [ACD] and lens thickness [LT]) using the IOLMaster 700, and one set of measurements (AL, Kmean and ACD) using the IOLMaster v3. Examiner 2 took one full set of measurements using the IOLMaster 700. Mean differences and 95% limits of agreement (LOA) were calculated, and Bland and Altman plots used to explore repeatability and reproducibility of the IOLMaster 700 alongside establishing its agreement with the IOLMaster v3.

Results

Mean participant age was 7.52 ± 0.58 years. Repeatability analyses demonstrated small mean differences and narrow 95% LOA for AL (0.001, −0.013 to 0.015 mm), Kmean (0.002, −0.020 to 0.024 mm), ACD (−0.003, −0.031 to 0.024 mm) and LT (0.001, −0.024 to 0.026 mm), respectively. Similarly, small mean differences and narrow 95% LOA established excellent reproducibility (AL 0.001, −0.016 to 0.018 mm; Kmean −0.001, −0.027 to 0.025 mm; ACD −0.010, −0.041 to 0.021 mm; LT 0.002, −0.016 to 0.020 mm). The IOLMaster 700 and IOLMaster v3 demonstrated good agreement with small mean differences and narrow 95% LOA (AL 0.009, −0.034 to 0.052 mm; Kmean 0.016, −0.013 to 0.044 mm; ACD 0.134, 0.055 to 0.212 mm).

Conclusions

When used within a paediatric population, these data demonstrate the IOLMaster 700 to be highly repeatable and reproducible for measures of AL, Kmean, ACD and LT. There is excellent inter‐instrument agreement between the IOLMaster 700 and IOLMaster v3 for measures of AL and Kmean. ACD measurements show weaker agreement. These data will be useful when considering reports from population‐based studies of refractive error and clinical myopia research.
Combigraft versus Bio‐Oss/Bio‐Gide in alveolar ridge preservation: A prospective randomized controlled trial
Authors: Hu Liru , Xiang Sijie , Liu Jiyuan , Ye Li , Cao Zhiwei , Pan Jian
Published: November 2021

The aim of this prospective study was to compare Combigraft with Bio‐Oss/Bio‐Gide complex in alveolar bone preservation in terms of clinical, laboratory and radiographic outcomes in a randomised controlled trial. 80 patients undergoing tooth extraction with the requirement of alveolar bone preservation were randomly allocated to the experimental and control groups. A total of 75 patients completed the study; 37 in the experimental group and 38 in the control group. Two patients who did not fully complete the study but had at least one record on the follow‐up period were analysed, significantly, 73 teeth among 77 dental sites were mandibular third molars which accounted for 94.8% of all subjects in this study. Bone grafting was performed using either of Combigraft or Bio‐Oss/Bio‐Gide complex. The primary outcome was to compare the height and width of alveolar ridge between immediate postoperation and six months postoperation by radiographic evaluation. A two‐sample t‐test was used for independent samples for quantitative variables (such as age) and a chi‐square statistic was used for nominal parameters. Six months after surgery, the height and width of alveolar ridge were 9.47 ± 1.61 mm and 14.71 ± 1.99 mm respectively using Combigraft while those were 9.82 ± 2.04 mm and 14.83 ± 2.04 mm respectively in the control group. There was no significant difference in the total effective rate between the two groups. Combigraft appears to be an alternative option to Bio‐Oss/Bio‐Gide complex for bone preservation in further clinical treatment. (No: CHiCTR19000230651).