bluuebunny/crossref_metadata_2025 huggingface dataset:
Heroism in the Age of Consumerism: The Emergence of a Moral Don Quixote in John Updike’s “A & P”
Authors: Bezdoode Zakarya , Bezdoode Eshaq
Published: February 2021

This paper analyzes John Updike’s short story “A & P” in the light of Max Weber’s notion of moral decision-making. A prominent contemporary American story-writer and literary critic, Updike has devoted his fiction to subjects’ rational and moral problems in the contemporary consumerist society. Updike’s lifelong probing into the middle classes’ lives is a body of fiction that raises questions about determinism, moral decision, and social responsibility, among others. “A & P” is a revealing example of such fiction and one among Updike’s most frequently anthologized short stories. The story, titled after a nationwide American shopping mall in the early twentieth century, investigates the possibility of decision-making within consumerist society. This paper demonstrates how Updike’s portrayal of his characters’ everyday lives reveals the predicament of intellectual thinking and moral decision-making in a consumerist society and warns against the loss of individual will in such societies.
Unseen Wounds
Authors: Bernhardt Fabian ,   DePaul University
Published: February 2021

Philosophical interest in vulnerability focusses mainly on normative questions concerning its relevance for moral, political and legal theory. However, beneath these questions there lies another one which is epistemological: How do we gain clear knowledge about another person’s pain and suffering? How do we recognize a wounded life? Drawing primarily on the account of Elaine Scarry (1984), the article aims at showing that the difficulties to apprehend and recognize a life as injured are not only grounded in political and cultural frames, as Judith Butler contends, but also in the phenomenological and epistemic features of pain itself. Pain is epistemically fragile. Whereas it is almost impossible to ignore one’s own pain, it is very easy to overlook the pain of others. This epistemic slope has concrete effects on the social and political life. Regarding vulnerability, the normative question of recognition and the epistemic question of recognizability, thus, are closely intertwined.
Weak Action
Authors: Bierhanzl Jan ,   DePaul University
Published: February 2021

The notion of “weak action” is developed in this paper in an attempt to overcome the schism between the action of a free political subject on the one hand, and their dependency on the support of others and the environment on the other. This paper focuses foremost on Judith Butler’s later work raising two different questions. First, following Butler and her critical reading of Levinas, the problem is raised how and at what price the ethics of vulnerability would be able to become not only the source of a critique of politics, but also the source of a concrete political action. Second, through Butler’s reinterpretation of Arendt’s political thinking, the notion of “action” is enriched by the dimension of vulnerability.
La investigación en pensamiento histórico. Un estudio a través de las tesis doctorales de Ciencias Sociales (1995-2020)
Authors: Chaparro Sainz Álvaro , Felices de la Fuente María del Mar , Triviño Cabrera Laura
Published: February 2021

Este artículo analiza la evolución de la investigación sobre pensamiento histórico a partir de las tesis doctorales nacionales e internacionales de los últimos veinticinco años. Para ello, se ha seguido un proceso sistemático de búsqueda en las principales bases de datos a nivel mundial, que ha reportado un total de 163 tesis doctorales. Estos trabajos se han analizado desde un enfoque metodológico cuantitativo descriptivo, con el programa de análisis estadístico SPSS y la herramienta Voyant Tools. Los resultados nos ofrecen información acerca del número de investigaciones realizadas, su evolución en el tiempo, los países, idiomas y universidades de mayor producción, y las principales temáticas trabajadas. Concluimos que, pese al aumento de las tesis doctorales sobre pensamiento histórico en los últimos años, continúan existiendo vacíos en la investigación apenas abordados.

In this article the evolution of research on Historical Thinking is analyzed based on national and international dissertations defended in the last twenty-five years. For this, we have followed a systematic search process in the main databases worldwide, which has reported a total of 163 dissertations. These works have been analyzed from a descriptive quantitative methodological approach, with the SPSS statistical analysis program and the Voyant Tools tool. The results offer us information about the number of researches carried out, their evolution over time, the countries, languages and universities with the highest production, and the main topics studied. We conclude that, despite the increase in doctoral thesis on Historical Thinking in recent years, there are still research gaps that have hardly been studied.
La historia de las personas: reflexiones desde la historiografía y de la didáctica de las ciencias sociales durante los últimos 25 años
Authors: Massip Sabater Mariona , Castellví Mata Jordi , Pagès Blanch Joan
Published: February 2021

En este artículo se revisa la evolución de la ciencia histórica y de la historia escolar a lo largo de los últimos 25 años. Esta revisión se centra en los avances en la investigación y la enseñanza de la historia de las personas; es decir, aquella que atiende a la totalidad de agentes sociales e históricos, que se articula a partir de la proyección global de la humanidad y que atiende a los problemas de las experiencias humanas. En primer lugar, se concreta el concepto de historia escolar y se explica la relación que se establece entre la historia escolar y la historiografía. En segundo lugar, se analiza la evolución de ambas a lo largo de estos 25 años. Finalmente, se plantean retos de futuro. Existe un desequilibrio entre la evolución del conocimiento histórico y el impacto que ha tenido en el currículo escolar. La historia escolar sigue centrada, de manera mayoritaria, en los procesos políticos nacionales, y reproduciendo saberes androcéntricos y eurocéntricos en los que se excluyen la gran mayoría de protagonistas.

In this article the evolution of historical science and school history over the past 25 years is reviewed. This review focuses on advances in people's history; that is, a history in which all social and historical agents are recognised, and which is articulated from the global consideration of humanity and human experiences. In the first place, the meaning of school history is specified, along with the relationship between school history and historiography. Secondly, the evolution of both over these 25 years is analysed. Finally, we pose future challenges.

There is an imbalance between the evolution of historical knowledge and the impact it has had on the school curriculum and educational practices. School history continues to reproduce androcentric and Eurocentric knowledge based on political processes in which the great majority of protagonists are excluded.
Une brève histoire de la politique de valorisation du patrimoine industriel en Belgique
Authors: Viaene Patrick
Published: February 2021

La Belgique ayant été le premier pays de l’Europe après l’Angleterre à connaître une industrialisation massive, il n’est pas étonnant d’y trouver aujourd’hui un patrimoine industriel d’une grande densité et d’une riche diversité. L’étude scientifique de ce patrimoine commence au début des années 1970, en particulier avec l’importante exposition « Le Règne de la Machine », organisée à Bruxelles en 1975. Mais la régionalisation des compétences culturelles (notamment), lancée dans les années 1980, ne facilite pas la sauvegarde de ce patrimoine et les projets de grande envergure. Pourtant, il importe de souligner l’importance croissante de certains musées industriels et de société comme le MIAT (Industriemuseum) à Gand, la Maison de la Métallurgie à Liège et La Fonderie à Bruxelles. Depuis les années 1990-2000, le patrimoine industriel s’inscrit dans les logiques d’attraction touristique qui se traduit par l’inscription de certains sites industriels belges dans la Liste du Patrimoine mondial de l’UNESCO. Depuis les deux dernières décennies, la recherche scientifique s’empare du phénomène et stimule les politiques de rénovation et de réaffectation durable d’anciens ensembles industriels et technologiques.
Patrimoine industriel et rapports de classes
Authors: Zanetti Thomas
Published: February 2021

Historiquement, le patrimoine et les monuments sont associés aux puissants, au contraire des catégories populaires. Dans le cas de l’industrie, la mise en patrimoine des héritages traduit fréquemment des rapports interclassistes de domination et d’exploitation. Mais la dimension spatiale des mémoires peut aussi constituer un moyen de dénonciation, de lutte et de résistance face aux inégalités sociales. La mémoire et le patrimoine sont donc des instruments de pouvoir sur et dans l’espace et des objets particulièrement pertinents pour analyser les relations entre groupes sociaux. Cet article s’appuie sur un ensemble de recherches menées depuis une quinzaine d’années et portant sur l’analyse des rapports de pouvoir dans la production des espaces urbains, saisis à partir des thématiques patrimoniales et mémorielles. Il cherche à montrer, à travers quatre cas d’études français, comment la patrimonialisation des héritages industriels renseigne sur les rapports socio-spatiaux de classes.
La place du patrimoine industriel dans les réhabilitations de friches
Authors: Gay Georges
Published: February 2021

Parce que leur requalification rencontre nécessairement le problème du traitement des traces de l’activité disparue, les friches questionnent le rapport que la société entretient avec le patrimoine industriel. Scories à éliminer car portant la marque de l’archaïsme pour les politiques fordistes d’aménagement, les héritages de l’industrialisation ancienne sont devenus des atouts à exploiter pour se distinguer dans la concurrence territoriale généralisée qui prévaut depuis les années 1980. L’instrumentalisation opportuniste du décor industriel qui marque les opérations alors engagées, rencontre ses limites au tournant des années 2000. L’émergence d’une sensibilité au patrimoine industriel dans les territoires concernés, la montée des contraintes environnementales, signent l’épuisement des recettes éprouvées. La mobilisation des ressources académiques apparaît alors comme un palliatif de l’impuissance des aménageurs. Il en résulte un approfondissement sur le sens historique du legs qui dépasse les effets de la seule séduction du bâti et transforme le statut du patrimoine de plus value dérobée en argument d’aménagement. Les logiques de requalification restent cependant essentiellement économiques et ne se démarquent pas d’objectifs de revalorisation et de promotion territoriale imposés aux populations.
Les acteurs privés et la réutilisation du patrimoine industriel en France
Authors: Rojas Luc
Published: February 2021

La réhabilitation et la réaffectation sont dans l’esprit des observateurs synonymes de l’action des acteurs publics. En effet, les grands projets de réhabilitations sont souvent portés et initiés par les municipalités et les intercommunalités. Or les acteurs privés (particuliers, entreprises, associations…) jouent un rôle important en matière de réhabilitation et de réaffectation. Ceux-ci peuvent être à l’initiative de la réhabilitation mais ils peuvent aussi investir un site réhabilité par les collectivités et offrir à celui-ci une seconde vie. L’ambition est ici de mettre à jour les motivations, les intérêts de l’acteur privé lorsqu’il prend en main la destinée d’un site : considère-t-il cet héritage comme une simple ressource foncière ou lui accorde-t-il plus de valeur? Cet article interroge aussi plus largement les caractéristiques de la réaffectation économique. Ainsi ce phénomène est aussi bien à l’initiative des collectivités que des acteurs privés. Néanmoins, des caractéristiques se dégagent, certains sites étant pris en charge par les municipalités et les intercommunalités alors que les autres sites restent en friche ou sont pris en charge par les entreprises, les particuliers ou les associations. Cependant tous posent la question de la patrimonialisation et de la valorisation.
La reconversion de l’Alliance, un site industriel d’exception en Haute-Loire (France)1
Authors: Garleff Jörn
Published: February 2021

Dans ces pages, Jörn Garleff, enseignant à l’Ecole Nationale d’architecture de Saint-Étienne, nous livre ses questions sur le site de L’Alliance situé à Pont-Salomon (Haute-Loire, France). Il est, en effet, depuis peu le président d’une association qui s’est donnée pour objectif de mettre en valeur ce site et de lui offrir une seconde vie par l’intermédiaire de projets. Ce témoignage, d’un acteur associatif essentiel en matière de patrimoine industriel, nous rappelle les difficultés et les interrogations inhérentes à une telle ambition.
Membrane-partitioned cell wall synthesis in mycobacteria
Authors: García-Heredia Alam , Kado Takehiro , Sein Caralyn E , Puffal Julia , Osman Sarah H , Judd Julius , Gray Todd A , Morita Yasu S , Siegrist M Sloan
Published: February 2021

Many antibiotics target the assembly of cell wall peptidoglycan, an essential, heteropolymeric mesh that encases most bacteria. In rod-shaped bacteria, cell wall elongation is spatially precise yet relies on limited pools of lipid-linked precursors that generate and are attracted to membrane disorder. By tracking enzymes, substrates, and products of peptidoglycan biosynthesis in Mycobacterium smegmatis, we show that precursors are made in plasma membrane domains that are laterally and biochemically distinct from sites of cell wall assembly. Membrane partitioning likely contributes to robust, orderly peptidoglycan synthesis, suggesting that these domains help template peptidoglycan synthesis. The cell wall-organizing protein DivIVA and the cell wall itself promote domain homeostasis. These data support a model in which the peptidoglycan polymer feeds back on its membrane template to maintain an environment conducive to directional synthesis. Our findings are applicable to rod-shaped bacteria that are phylogenetically distant from M. smegmatis, indicating that horizontal compartmentalization of precursors may be a general feature of bacillary cell wall biogenesis.
Coupling between fast and slow oscillator circuits in Cancer borealis is temperature-compensated
Authors: Powell Daniel , Haddad Sara A , Gorur-Shandilya Srinivas , Marder Eve
Published: February 2021

Coupled oscillatory circuits are ubiquitous in nervous systems. Given that most biological processes are temperature-sensitive, it is remarkable that the neuronal circuits of poikilothermic animals can maintain coupling across a wide range of temperatures. Within the stomatogastric ganglion (STG) of the crab,Cancer borealis, the fast pyloric rhythm (~1 Hz) and the slow gastric mill rhythm (~0.1 Hz) are precisely coordinated at ~11°C such that there is an integer number of pyloric cycles per gastric mill cycle (integer coupling). Upon increasing temperature from 7°C to 23°C, both oscillators showed similar temperature-dependent increases in cycle frequency, and integer coupling between the circuits was conserved. Thus, although both rhythms show temperature-dependent changes in rhythm frequency, the processes that couple these circuits maintain their coordination over a wide range of temperatures. Such robustness to temperature changes could be part of a toolbox of processes that enables neural circuits to maintain function despite global perturbations.
Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success
Authors: Heier Christoph , Knittelfelder Oskar , Hofbauer Harald F , Mende Wolfgang , Pörnbacher Ingrid , Schiller Laura , Schoiswohl Gabriele , Xie Hao , Grönke Sebastian , Shevchenko Andrej , Kühnlein Ronald P
Published: February 2021

Triacylglycerol (TG) and steryl ester (SE) lipid storage is a universal strategy to maintain organismal energy and membrane homeostasis. Cycles of building and mobilizing storage fat are fundamental in (re)distributing lipid substrates between tissues or to progress ontogenetic transitions. In this study, we show that Hormone-sensitive lipase (Hsl) specifically controls SE mobilization to initiate intergenerational sterol transfer inDrosophila melanogaster. Tissue-autonomous Hsl functions in the maternal fat body and germline coordinately prevent adult SE overstorage and maximize sterol allocation to embryos. While Hsl-deficiency is largely dispensable for normal development on sterol-rich diets, animals depend on adipocyte Hsl for optimal fecundity when dietary sterol becomes limiting. Notably, accumulation of SE but not of TG is a characteristic of Hsl-deficient cells across phyla including murine white adipocytes. In summary, we identified Hsl as an ancestral regulator of SE degradation, which improves intergenerational sterol transfer and reproductive success in flies.
Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
Authors: Eastwood Evelyn L , Jara Kayla A , Bornelöv Susanne , Munafò Marzia , Frantzis Vasileios , Kneuss Emma , Barbar Elisar J , Czech Benjamin , Hannon Gregory J
Published: February 2021

In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.
Search, access, and explore life science nanopublications on the Web
Authors: Giachelle Fabio , Dosso Dennis , Silvello Gianmaria
Published: February 2021

Nanopublications are Resource Description Framework (RDF) graphs encoding scientific facts extracted from the literature and enriched with provenance and attribution information. There are millions of nanopublications currently available on the Web, especially in the life science domain. Nanopublications are thought to facilitate the discovery, exploration, and re-use of scientific facts. Nevertheless, they are still not widely used by scientists outside specific circles; they are hard to find and rarely cited. We believe this is due to the lack of services to seek, find and understand nanopublications’ content. To this end, we present the NanoWeb application to seamlessly search, access, explore, and re-use the nanopublications publicly available on the Web. For the time being, NanoWeb focuses on the life science domain where the vastest amount of nanopublications are available. It is a unified access point to the world of nanopublications enabling search over graph data, direct connections to evidence papers, and scientific curated databases, and visual and intuitive exploration of the relation network created by the encoded scientific facts.
OPTICAL+: a frequency-based deep learning scheme for recognizing brain wave signals
Authors: Kumar Shiu , Sharma Ronesh , Sharma Alok
Published: February 2021

A human–computer interaction (HCI) system can be used to detect different categories of the brain wave signals that can be beneficial for neurorehabilitation, seizure detection and sleep stage classification. Research on developing HCI systems using brain wave signals has progressed a lot over the years. However, real-time implementation, computational complexity and accuracy are still a concern. In this work, we address the problem of selecting the appropriate filtering frequency band while also achieving a good system performance by proposing a frequency-based approach using long short-term memory network (LSTM) for recognizing different brain wave signals. Adaptive filtering using genetic algorithm is incorporated for a hybrid system utilizing common spatial pattern and LSTM network. The proposed method (OPTICAL+) achieved an overall average classification error rate of 30.41% and a kappa coefficient value of 0.398, outperforming the state-of-the-art methods. The proposed OPTICAL+ predictor can be used to develop improved HCI systems that will aid in neurorehabilitation and may also be beneficial for sleep stage classification and seizure detection.
The natural product biosynthetic potential of Red Sea nudibranch microbiomes
Authors: Abdelrahman Samar M. , Patin Nastassia V. , Hanora Amro , Aboseidah Akram , Desoky Shimaa , Desoky Salha G. , Stewart Frank J. , Lopanik Nicole B.
Published: February 2021

Background

Antibiotic resistance is a growing problem that can be ameliorated by the discovery of novel drug candidates. Bacterial associates are often the source of pharmaceutically active natural products isolated from marine invertebrates, and thus, important targets for drug discovery. While the microbiomes of many marine organisms have been extensively studied, microbial communities from chemically-rich nudibranchs, marine invertebrates that often possess chemical defences, are relatively unknown.

Methods

We applied both culture-dependent and independent approaches to better understand the biochemical potential of microbial communities associated with nudibranchs. Gram-positive microorganisms isolated from nudibranchs collected in the Red Sea were screened for antibacterial and antitumor activity. To assess their biochemical potential, the isolates were screened for the presence of natural product biosynthetic gene clusters, including polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, using PCR. The microbiomes of the nudibranchs were investigated by high-throughput sequencing of 16S rRNA amplicons.

Results

In screens against five model microorganisms, 51% of extracts displayed antimicrobial activity against more than one organism, and 19% exhibited antitumor activity against Ehrlich’s ascites carcinoma. Sixty-four percent of isolates contained PKS and NRPS genes, suggesting their genomes contain gene clusters for natural product biosynthesis. Thirty-five percent were positive for more than one class of biosynthetic gene. These strains were identified as belonging to the Firmicutes and Actinobacteria phyla via 16S rRNA gene sequencing. In addition, 16S rRNA community amplicon sequencing revealed all bacterial isolates were present in the uncultured host-associated microbiome, although they were a very small percentage of the total community. Taken together, these results indicate that bacteria associated with marine nudibranchs are potentially a rich source of bioactive compounds and natural product biosynthetic genes.
A Rare Case of Coexistence of Homozygous β-Thalassaemia and Glucose 6 Phosphate Dehydrogenase Deficiency
Authors: Khunger Jitendar Mohan , Gupta Monika , Jain Ankur , Malhotra Monica Khunger
Published: February 2021

β-thalassaemia is one of the most prevalent autosomal disorders worldwide. Mutations/deletions in globin gene underlie deficiencies in Haemoglobin (Hb) production, which can interfere with oxygen delivery by Hb, resulting in thalassaemias causing anaemias with a wide range of disease severity. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is a genetic abnormality resulting in inadequate amount of G6PD in the Red Blood Cells (RBCs). In patients with G6PD deficiency, the reduced or absent activity of the enzyme in RBCs causes premature haemolysis and symptomatic anaemia. The marked oxidative stress caused by homozygous β-thalassaemia is apparently incompatible with G6PD deficiency. Here, a rare case of six-month-old male child is described who presented with severe pallor hepato-splenomegaly and these two conditions co-existed in this patient.
Paediatric Embryonal Tumours in Multilayered Rosettes Presenting as a Low Grade Glioma- An Unusual Case Report
Authors: Ganapathy Sibhi , Godhani Nikunj
Published: February 2021

Paediatric Embryonal Tumours in Multilayered Rosettes (ETMR) are rare aggressive tumours with poor survival statistics, defined in 2016 by World Health Organisation (WHO) classification of brain tumours. The tumours have a characteristic radiological appearance on Magnetic Resonance Imaging (MRI) of the brain, which is easily decipherable. This combined with a clinical picture of raised intracranial pressure symptoms, seizures and rapidly progressive new onset neurological deficits make the diagnosis fairly obvious. The final confirmation of the diagnosis is done by immunohistochemical analysis of the C19Myc gene alteration. Rarely, certain radiological presentations are uncharacteristic and resemble other more benign pathologies with overlapping clinical presentations. This can be misleading, as ETMRs require aggressive surgery followed by adjuvant chemotherapy and radiation to ensure best possible survival. We present such a case report of what appeared to be a low-grade glioma in the frontal lobe. This tumour presented with one episode of generalised tonic clonic seizures not unusual as a presenting complaint in low-grade gliomas per se. Surgical debulking under ultrasonic guidance was done and the specimen was sent to histopathological analysis. The histopathological analysis showed a surprise ETMR diagnosis which was sent for confirmation to two other centers. This case report highlights the need to keep ETMRs as a rare differential diagnosis for even low-grade gliomas of the brain, thereby allowing accurate prognostication only after histopathological and immunohistochemical assessment. We present a brief literature review on unusual presentations of ETMRs reported in literature to further illustrate the chimeric nature of this rare disease.
Effects of Momordica Charantia Seed Extract on Dexamethasone-Induced Biochemical and Histological Abnormalities in Albino Rats
Authors: Rajesh Dasaraju , Thejaswini Muppala , Advaitha MV
Published: February 2021

Introduction: Many preclinical studies and randomised trials in humans have documented the antidiabetic properties of bitter melon, Momordica charantia (M. charantia). Aim: To examine the effects of Momordica CharantiaSeed Extract (MCSE) in comparison to Pioglitazone on Dexamethasone-induced biochemical and histological abnormalities in Albino rats. Materials and Methods: An interventional study was conducted from October, 2015 to December, 2015, with 24 adult healthy Albino rats of Wistar strain, which were divided into four groups of six rats each. Group I (diabetic controls) received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for six days to induce metabolic changes. Group II rats received MCSE 2.5g/kg six days before dexamethasone and six days during dexamethasone administration. Group III rats received pioglitazone 75 mg/kg orally six days before dexamethasone and six days during dexamethasone administration. Rats in Group IV did not receive any medication and was considered as normal control. Blood glucose levels and lipid profiles were measured. Liver weight, liver volume, and histopathological analysis were done. Data were analysed using an Independent t-test followed by ANOVA with Scheffe’s Post-Hoc Test. Statistical significance was set at p<0.05. Results: A significant decrease in the Fasting Blood Sugar and Postprandial Blood Sugar levels was observed in the MCSE and pioglitazone-treated groups as compared to the dexamethasone control group (p<0.01). A significant decrease in the total cholesterol and triglycerides and an increase in High Density Lipoprotein (HDL) levels was observed in MCSE and pioglitazone-treated groups as compared to the dexamethasone control group (p<0.01). In the case of dexamethasone-induced diabetic model, both MCSE and pioglitazone significantly reduced hepatomegaly, dyslipidemia, and hyperglycaemia (p<0.01). Conclusion: MCSE has comparable efficacy to pioglitazone in the prevention of dexamethasone-induced hepatomegaly, dyslipidemia, and hyperglycaemia.
IMP3 Expression in Ovarian Serous Tumours: Correlation with Epithelial-Mesenchymal Transition-Related Markers (E-Cadherin and Vimentin) and Clinicopathological Factors
Authors: Elbasateeny Samah Said , Elnagar Walid Mohamed , Yassin Mahmoud Abdou , Rashad Heba Mohammed
Published: February 2021

Introduction: Ovarian epithelial cancer is an aggressive malignancy of which Ovarian Serous Carcinoma (OSC) represents a common type. The insulin-like growth factor mRNA-binding protein 3 (IMP3) is one of mRNA-binding protein family that is overexpressed in a variety of human cancers, including ovarian carcinomas. Being associated with adverse prognostic outcome in these cancers, which makes this protein a reliable biomarker to distinguish some cancers from their benign mimetic lesions. Aim: To analyse IMP3 expression in serous ovarian tumours and correlates the expression in malignant tumours with Epithelio-Mesenchymal Transition (EMT) related markers (Epithelial(E)-cadherin and vimentin) and clinicopathological factors to assess the clinical application of IMP3 in the diagnosis, prognosis and possible application in targeted therapy of such tumours. Materials and Methods: This was a cross-sectional research that was done at the Departments of Pathology, Obstetric and Surgery, Zagazig and Banha Universities Hospitals, Egypt. Fifty-nine formalin-fixed paraffin-embedded specimens (including 43 cases OSC, 6 cases border line serous tumour and 10 cases benign serous cystadenoma) were collected from January 2014 to December 2018. Each case was stained immunohistochemically with IMP3, E-cadherin and Vimentin. Markers expressions were statistically analysed using SPSS software (version 19.0; SPSS, Chicago, IL). The p-values ≤0.05 was regarded statistically significant. Results: IMP3 was detected in 76.7% (33/43) of the studied OSC. IMP3 was in a significant association with advanced FIGO (International Federation of Gynaecology and Obstetrics) stage and with lymph node metastases (p=0.02 and 0.019, respectively). E-cadherin was predominantly lost in 53.5% (23/43) of the studied OSCs and was significantly associated with advanced FIGO stage (p=0.004). Vimentin was detected in 79.1% (34/43) of the studied OSCs and was in association with high grades and advanced stage (p=0.018 and 0.007, respectively). An inverse significant correlation was detected between IMP3 and E-cadherin expressions (Spearman correlation (r)=-0.480, p-value=0.001), while positive significant correlation was detected between IMP3 and Vimentin expressions (Spearman correlation (r)=0.393, p-value=0.009). Conclusion: IMP3 is an oncogene unregulated in OSC. It is a prognostic marker associated with tumour aggressiveness. Moreover, IMP3 could promote tumour invasion and metastasis via EMT in OSCs.
Drug‐induced liver injury in the era of biologics: The case of natalizumab
Authors: Taveira Filipe , Lopes Sandra , Faria Carlos , Mendes Sofia , Figueiredo Pedro
Published: February 2021

Drug‐induced liver injury (DILI) is a challenging diagnosis regarding the complexity of mechanisms, drugs, supplements, and herbs that can have hepatotoxic potential. Biologics are increasing as common drugs in the treatment of chronic inflammatory diseases and some DILI were previously reported with those agents. Natalizumab, a recombinant monoclonal antibody used for the treatment of multiple sclerosis (MS) has a good safety profile with extremely rare liver‐related adverse events. The clinical case of a 44‐year‐old female with the history of MS and the recent start of natalizumab was reported. The patient was admitted with jaundice, choluria, fatigue, anorexia, nausea, and diffuse abdominal discomfort. No signs of encephalopathy or MS flare on examination. Laboratory values: aspartate aminotransferase, 905 U/L; alanine transaminase, 1559 U/L; ALP, 127 U/L; GGT, 301 U/L; total bilirubin, 12.8 mg/dL; direct bilirubin, 5.9 mg/dL, Albumin 2.9 g/dL, platelet 137 g/L, and 2.44 INR. No infectious, vascular, metabolic causes, or biliary obstruction were found. Liver biopsy suggested toxic hepatitis with autoimmune features. Since no definite criteria for autoimmune hepatitis (AH) were met, steroids were not given. The patient was on supportive measures and was presented to a liver transplant unit. Therefore, DILI due to natalizumab was assumed and its discontinuation led to the resolution of all symptoms in a 6‐month window. The increasingly common use of biological therapy or with direct influence on the immune system should raise the suspicion of the gastroenterologist in all cases of suspected DILI.
Biochemical‐ and Biophysical‐Induced Barriergenesis in the Blood–Brain Barrier: A Review of Barriergenic Factors for Use in In Vitro Models
Authors: Schofield Christina L. , Rodrigo-Navarro Aleixandre , Dalby Matthew J. , Van Agtmael Tom , Salmeron-Sanchez Manuel
Published: February 2021

Central nervous system (CNS) pathologies are a prevalent problem in aging populations, creating a need to understand the underlying events in these diseases and develop efficient CNS‐targeting drugs. The importance of the blood–brain barrier (BBB) is evident, acting both as a physical barrier to drug entry into the CNS and potentially as the cause or aggravator of CNS diseases. The development of a biomimetic BBB in vitro model is required for the understanding of BBB‐related pathologies and in the screening of drugs targeting the CNS. There is currently great interest in understanding the influence of biochemical and biophysical factors, as these have the potential to greatly improve the barrier function of brain microvascular endothelial cells (BMECs). Recent advances in understanding how these may regulate barriergenesis in BMECs help promote the development of improved BBB in vitro models and therefore novel interventional therapies for pathologies related to its disruption. Herein, an overview of specific biochemical and biomechanical cues in the formation of the BBB, with a focus on in vitro models and how these might recapitulate the BBB function, is provided.
Predictive ability of four small‐scale quality tests for dough rheological properties and baking quality in hard red spring wheat
Authors: Daba Sintayehu D. , Simsek Senay , Green Andrew J.
Published: February 2021

Background and Objectives

Predictive models for use in early generation hard spring wheat breeding were evaluated for Farinograph and baking quality. Flour samples were prepared on the Quadrumat Jr. and Buhler mill from 48 genotypes grown at four locations in North Dakota.

Findings

Models developed from 13 predictor variables from GlutoPeak, Glutomatic, Near Infrared Reflectance (NIR), and Solvent Retention Capacity (SRC) predicted Farinograph water absorption (ABS) and baking absorption (BA) with cross‐validated prediction accuracies of 0.71 and 0.58, respectively. For Farinograph peak time (PT), Farinograph Stability (STAB), mixing time (MT), and loaf volume (LV), the prediction accuracies were high in the model development dataset (r2 ranging from 0.60 to 0.76). However, in the cross‐validation set, the prediction accuracies only ranged from 0.30 to 0.48.

Conclusions

GlutoPeak parameters can be used to predict ABS and BA in early breeding stages. Prediction of stability and peak time showed potential, and models should be improved to better predict mixing time and loaf volume.

Significance and novelty

Results from a multi‐location trial involving a large number of genotypes are needed to validate the prediction accuracy for end‐use traits in hard red spring wheat. Comparing results from different mill types and diverse genotypes ensures broad applicability.
Pharmacokinetics and Safety of Dapoxetine Hydrochloride in Healthy Chinese Men: Impact of Dose and High‐Fat Meal
Authors: Liu Jingyan , Li Zhihui , Yan Keyu , Ju Gehang , Qiu Wen
Published: February 2021

Dapoxetine is the first oral medication specifically developed for the on‐demand treatment of premature ejaculation. The pharmacokinetics and safety of 30 mg (n = 40) and 60 mg (n = 38) dapoxetine in healthy Chinese under fasted and fed states were assessed in 2 studies. Both studies are random, single‐center, 2‐period, open‐label, 2‐way crossover designs. Plasma concentration of dapoxetine was determined by high‐performance liquid chromatography–tandem mass spectrometry, and the pharmacokinetic parameters were calculated using noncompartmental analysis. Dapoxetine was quickly absorbed and reached maximum concentration 1 to 3 hours after oral administration. Elimination was biphasic, and the plasma concentration decreased to 3% to 7% of maximum concentration by 24 hours while half‐life was 15 to 18 hours. Meantime, high‐fat meals slightly increased its exposure. Both doses of dapoxetine were well tolerated. The adverse events in the high‐dose group under fasted and fed states were 37.9% and 19.0%, respectively.
Transformation of Corn Lignin into Sun Cream Ingredients
Authors: Yang See Jie , Song Song , Xiao Yiying , Trang Pham Thuy , Zhao Yu , Lapkin Alexei , Yan Ning
Published: February 2021

Production of value‐added chemicals from lignocellulose is one of the key strands of the emerging bio‐economy. A synthetic approach has been developed to produce p‐methoxy coumarate esters from waste corn stover and corn bran, and further transform these compounds into consumer products. In the first step, p‐coumaric acid (pCA) and ferulic acid (FA) are released through mild alkaline hydrolysis of corn waste, in more than 20 mg g−1 yield (10 wt % based on lignin content). Subsequently, heterogeneous solid acids catalyze the esterification of pCA with various alcohols. Amberlite IR‐15 shows the best catalytic performance, owing to its optimal acid density, large surface area, and suitable pore diameter. The solid acid catalyst can be recycled with slight activity loss and regenerated by acid washing and vacuum drying. Finally, methylation of p‐coumarate ester to give target product p‐methoxy coumarate esters is carried out by using commercially available and low‐cost inorganic bases (e. g., K2CO3). Base‐catalyzed transesterification of methyl p‐methoxy coumarate to p‐methoxy coumarate esters is also investigated.
Intensification of Photobiocatalytic Decarboxylation of Fatty Acids for the Production of Biodiesel
Authors: Duong Hong T. , Wu Yinqi , Sutor Alexander , Burek Bastien O. , Hollmann Frank , Bloh Jonathan Z.
Published: February 2021

Light‐driven biocatalytic processes are notoriously hampered by poor penetration of light into the turbid reaction media. In this study, wirelessly powered light‐emitting diodes are found to represent an efficient and scalable approach for process intensification of the photobiosynthetic production of diesel alkanes from renewable fatty acids.
The trickle‐down effect of procedural fairness on perceptions of daily discrimination: How societal actors can build social trust among minority members
Authors: Dierckx Kim , Valcke Barbara , Van Hiel Alain
Published: February 2021

The present research investigated the trickle‐down effect of procedural fairness enacted by societal institutions on minority members’ social trust. Building on the racial identity development hypothesis, we argued that procedural fairness represents a racial socialization experience, which influences how minorities perceive discrimination in daily life. Perceived group discrimination, in turn, impacts social trust. The results of five studies with African American samples corroborated the hypothesized mediation model. Study 1 showed that minority members distinctly perceive fairness enacted by institutions and discrimination by fellow citizens. Subsequent studies demonstrated that manipulating procedural fairness influenced perceived discrimination in an “attribution‐to‐discrimination” paradigm (Study 2), and that inducing discrimination lowered trust in an allocation game (Study 3). Finally, Studies 4 and 5 obtained cross‐sectional evidence for the full model. Our results thus contribute to literature by showing that perceived discrimination mediates the relationship between procedural fairness and social trust. Societally relevant practical implications are discussed.
Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines
Authors: Yang Youfeng , Ricketts Christopher J. , Vocke Cathy D. , Killian J. Keith , Padilla‐Nash Hesed M. , Lang Martin , Wei Darmood , Lee Young H. , Wangsa Darawalee , Sourbier Carole , Meltzer Paul S. , Ried Thomas , Merino Maria J. , Metwalli Adam R. , Ball Mark W. , Srinivasan Ramaprasad , Linehan W. Marston
Published: February 2021

Renal cell carcinoma (RCC) is not a single disease but is made up of several different histologically defined subtypes that are associated with distinct genetic alterations which require subtype specific management and treatment. Papillary renal cell carcinoma (pRCC) is the second most common subtype after conventional/clear cell RCC (ccRCC), representing ~20% of cases, and is subcategorized into type 1 and type 2 pRCC. It is important for preclinical studies to have cell lines that accurately represent each specific RCC subtype. This study characterizes seven cell lines derived from both primary and metastatic sites of type 1 pRCC, including the first cell line derived from a hereditary papillary renal carcinoma (HPRC)‐associated tumor. Complete or partial gain of chromosome 7 was observed in all cell lines and other common gains of chromosomes 16, 17, or 20 were seen in several cell lines. Activating mutations of MET were present in three cell lines that all demonstrated increased MET phosphorylation in response to HGF and abrogation of MET phosphorylation in response to MET inhibitors. CDKN2A loss due to mutation or gene deletion, associated with poor outcomes in type 1 pRCC patients, was observed in all cell line models. Six cell lines formed tumor xenografts in athymic nude mice and thus provide in vivo models of type 1 pRCC. These type 1 pRCC cell lines provide a comprehensive representation of the genetic alterations associated with pRCC that will give insight into the biology of this disease and be ideal preclinical models for therapeutic studies.
Institutional quality and social cost of intermediation in Africa: Does the level of financial market development matter?
Authors: Karikari Nana Kwasi , Gyan Kwadwo Kwakye , Khan Muhammad Ahad Hayat , Kusi Baah Aye
Published: February 2021

This article examines the effect of institutional quality on social cost of intermediation in high and low developed financial markets across 29 African countries between 2006 and 2013. Employing bootstrap‐quantile and two‐step system generalized methods of moments models with bank level data of about 330 banks, the results provide interesting and new insights. The results show that improvement in institutional quality in high or low developed financial markets translates into reduced social cost of intermediation to the society. However, it is evident from the results that improvement in institutional quality is more robust, persistent and weightier in reducing the social cost of intermediation in low developed financial markets which are often characterized with weak regulatory regimes and enforcement. Hence, improvement in institutional quality shores up regulatory supervision, monitoring and enforcement which translates into heavier dampening of social cost of financial intermediation in less developed financial markets. Moreover, bank size, credit shocks, return on equity and liquidity are key drives of social cost of intermediation both in low and high developed financial markets. These findings have policy implications and recommendations for policymakers and regulators of financial institutions. Policymakers and regulators, especially those in less developed financial markets, must endeavour to create, implement and advance mechanisms and enabling environment that enhances the quality of institutions since improved institutional quality reduces social cost of intermediation to the benefit of society.
Role of endocytosis and trans-endocytosis in ICOS costimulator-induced downmodulation of the ICOS Ligand
Authors: Aragoneses-Fenoll Laura , Montes-Casado María , Ojeda Gloria , García-Paredes Lucía , Arimura Yutaka , Yagi Junji , Dianzani Umberto , Portolés Pilar , Rojo José M
Published: February 2021

The interaction between the T-lymphocyte costimulatory molecule ICOS and its ligand (ICOS-L) is needed for efficient immune responses, but expression levels are tightly controlled, as altered expression of ICOS or ICOS-L may lead to immunodeficiency, or favor autoimmune diseases and tumor growth.

Using cells of mouse B cell lymphoma (M12.C3) and melanoma (B16), or hamster CHO cells transfected with various forms of mouse ICOS-L, and ICOS+ T cell lines, we show that, within minutes, ICOS induces significant downmodulation of surface ICOS-L that is largely mediated by endocytosis and trans-endocytosis. So, after interaction with ICOS+ cells, ICOS-L was found inside permeabilized cells, or in cell lysates, with significant transfer of ICOS from ICOS+ T cells to ICOS-L-expressing cells, and simultaneous loss of surface ICOS by the T cells. Data from cells expressing ICOS-L mutants show that conserved, functionally important residues in the cytoplasmic domain of mouse ICOS-L (Arg300, Ser307 and Tyr308), or removal of ICOS-L cytoplasmic tail have minor effect on its internalization.

Internalization was dependent on temperature, and was partially dependent on actin polymerization, the GTPase dynamin, protein kinase C, or the integrity of lipid rafts. In fact, a fraction of ICOS-L was detected in lipid rafts. On the other hand, proteinase inhibitors had negligible effects on early modulation of ICOS-L from the cell surface.

Our data add a new mechanism of control of ICOS-L expression to the regulation of ICOS-dependent responses.
Diabetes predicts severity of COVID‐19 infection in a retrospective cohort: A mediatory role of the inflammatory biomarker C‐reactive protein
Authors: Koh Huilin , Moh Angela Mei Chung , Yeoh Ester , Lin Yi , Low Serena Kiat Mun , Ooi Say Tat , Tan Seng Kiong , Lin Jaime Hui Xian , Hoong Caroline Wei Shan
Published: February 2021

Diabetes is a risk factor for developing severe COVID‐19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID‐19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID‐19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%–6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID‐19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID‐19 outcome was analyzed by cox regression. Adjusted mediation analysis of C‐reactive protein (CRP) on the relationship between diabetes and severe COVID‐19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID‐19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID‐19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54–17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92–8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22–4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID‐19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID‐19 infection, confirming that inflammation is important in the pathogenesis of severe COVID‐19 in diabetes.