bluuebunny/crossref_metadata_2025 huggingface dataset:
Elizabeth Bowen and Eudora Welty: Selected Correspondence
Authors: Hepburn Allan
Published: April 2021

Over her career, Elizabeth Bowen published ten novels, yet she left no comprehensive theory of the novel. This essay draws especially upon ‘Notes on Writing a Novel’ (1945), ‘The Technique of the Novel’ (1953), and ‘Truth and Fiction’ (1956), as well as opinions that Bowen expressed in her weekly book columns for The Tatler, to formulate her key perceptions of, and rules for, writing a novel. Bowen defined her ideas by drawing upon the empirical evidence of novels by Elizabeth Taylor, Olivia Manning, H.E. Bates, Jane Austen, Gustave Flaubert, and numerous others. She gave particular thought to ‘situation’, by which she means the central problematic or the crux of the story. The situation precedes and fuels plot. The Second World War, Bowen claimed in her essays and reviews, had a decisive influence on heroism and contemporary fiction by heightening its scale and its repertory of situations.
Endometriosis of the Rectus Abdominis Muscle: A Rare Cause of Emergency Department Visit; Case Report
Authors: Seyit Murat , Sonmez Yalcin , Yilmaz Atakan , Ozen Mert
Published: April 2021

Introduction: Endometriosis affects approximately 10% of the reproductive age woman. Although the most common affected sites are ovaries, sacrouterine ligament, rectovaginal septum, and pelvic peritoneum, it can be located in any organ. Endometriosis of rectus abdominal muscle independent from the cesarean section incision is extremely rare.

Case Presentation: A 31-years-old female was admitted to the emergency department with periodical abdominal pain and distension complaints. Ultrasonography and computed tomography revealed a heterogeneous mass in the rectus abdominis muscle. Surgical excision was performed. Histopathologic examination showed endometrial tissue with glandular and stromal elements within the muscularis propria.

Conclusion: Endometriosis should be kept in mind in the differential diagnosis of atypical pain and mass of the abdominal wall in the emergency settings.
Sensitivity analysis on the impact of geometrical and operational variations on turbine hub cavity modes and practical methods to control them
Authors: Iranidokht Vahid , Kalfas Anestis , Abhari Reza , Senoo Shigeki , Momma Kazuhiro
Published: April 2021

This paper presents an experimental investigation on the impact of different design and operational variations on the instabilities induced at the hub cavity outlet of a turbine. The experiments were conducted at the “LISA” test facility at ETH Zurich. The axial gap at the 2nd stage hub cavity exit was varied, and also three different flow deflectors were implemented at the cavity exit to control the cavity modes (CMs). Furthermore, the turbine pressure ratio was altered to mimic the off-design condition and study the sensitivity of the CMs to this parameter. Measurements were performed using pneumatic, and Fast Response Aerodynamic Probes (FRAP) at stator and rotor exit. In addition, unsteady pressure transducers were installed at the cavity exit wall to measure the characteristic parameters of the CMs.
For the small axial gap, distinct and strong CMs were generated, which actively interacted with stator and rotor hub flow structures. Increasing the gap damped the fluctuations; however, a broader range of frequencies was amplified. The flow deflectors successfully suppressed the CMs by manipulating the shear layer velocity profile and blocking the growing instabilities. Eventually, the increase in the turbine pressure ratio strengthened the CMs and vice versa.
USING OUTLINING STRATEGY IN ESSAY WRITING FOR ELT STUDENTS’
Authors: Al Islamiah Siti Fatimah , Sari Dina Merris Maya
Published: April 2021

This research discusses the outlining strategy that applied in the ELT students’ essay writing class 2019 A English Education Program STKIP PGRI Sidoarjo which amounted to 10 students. The instruments used in this study were checklist observation and questionnaires. The data technique used is qualitative data, where the data will be described. The first research instrument, the researcher used a checklist observation form for implementation assessment by observing the class writing essays and participating in learning activities from beginning to end whose data was described in a table with a tick, the results showed that many activities were carried out by students in the classroom to improve their abilities in writing essays through an outlining strategy. The next instrument is a questionnaire for response assessment, the researcher asks for data from ELT students via a google form containing 15 yes or no questions. The results of the questionnaire showed that 90% of students answered yes, and 10% of students answered no. The results showed that the implementation and response of students were very positive and good during the learning activities to write essays using the outlining strategies of ELT students.
A Chemo-Genomic Approach Identifies Diverse Epigenetic Therapeutic Vulnerabilities in MYCN-Amplified Neuroblastoma
Authors: Krstic Aleksandar , Konietzny Anja , Halasz Melinda , Cain Peter , Oppermann Udo , Kolch Walter , Duffy David J.
Published: April 2021

Although a rare disease, neuroblastoma accounts for the highest proportion of childhood cancer deaths. There is a lack of recurrent somatic mutations in neuroblastoma embryonal tumours, suggesting a possible role for epigenetic alterations in driving this cancer. While an increasing number of reports suggest an association of MYCN with epigenetic machinery, the mechanisms of these interactions are poorly understood in the neuroblastoma setting. Utilising chemo-genomic approaches we revealed global MYCN-epigenetic interactions and identified numerous epigenetic proteins as MYCN targets. The epigenetic regulators HDAC2, CBX8 and CBP (CREBBP) were all MYCN target genes and also putative MYCN interactors. MYCN-related epigenetic genes included SMARCs, HDACs, SMYDs, BRDs and CREBBP. Expression levels of the majority of MYCN-related epigenetic genes showed predictive ability for neuroblastoma patient outcome. Furthermore, a compound library screen targeting epigenetic proteins revealed broad susceptibility of neuroblastoma cells to all classes of epigenetic regulators, belonging to families of bromodomains, HDACs, HATs, histone methyltransferases, DNA methyltransferases and lysin demethylases. Ninety-six percent of the compounds reduced MYCN-amplified neuroblastoma cell viability. We show that the C646 (CBP-bromodomain targeting compound) exhibits switch-like temporal and dose response behaviour and is effective at reducing neuroblastoma viability. Responsiveness correlates with MYCN expression, with MYCN-amplified cells being more susceptible to C646 treatment. Thus, exploiting the broad vulnerability of neuroblastoma cells to epigenetic targeting compounds represents an exciting strategy in neuroblastoma treatment, particularly for high-risk MYCN-amplified tumours.
Slit/Robo Signaling Regulates Multiple Stages of the Development of the Drosophila Motion Detection System
Authors: Guzmán-Palma Pablo , Contreras Esteban G. , Mora Natalia , Smith Macarena , González-Ramírez M. Constanza , Campusano Jorge M. , Sierralta Jimena , Hassan Bassem A. , Oliva Carlos
Published: April 2021

Neurogenesis is achieved through a sequence of steps that include specification and differentiation of progenitors into mature neurons. Frequently, precursors migrate to distinct positions before terminal differentiation. The Slit-Robo pathway, formed by the secreted ligand Slit and its membrane bound receptor Robo, was first discovered as a regulator of axonal growth. However, today, it is accepted that this pathway can regulate different cellular processes even outside the nervous system. Since most of the studies performed in the nervous system have been focused on axonal and dendritic growth, it is less clear how versatile is this signaling pathway in the developing nervous system. Here we describe the participation of the Slit-Robo pathway in the development of motion sensitive neurons of theDrosophila visualsystem. We show that Slit and Robo receptors are expressed in different stages during the neurogenesis of motion sensitive neurons. Furthermore, we find that Slit and Robo regulate multiple aspects of their development including neuronal precursor migration, cell segregation between neural stem cells and daughter cells and formation of their connectivity pattern. Specifically, loss of function ofslitorroboreceptors in differentiated motion sensitive neurons impairs dendritic targeting, while knocking downroboreceptors in migratory progenitors or neural stem cells leads to structural defects in the adult optic lobe neuropil, caused by migration and cell segregation defects during larval development. Thus, our work reveals the co-option of the Slit-Robo signaling pathway in distinct developmental stages of a neural lineage.
Quantum Mechanical Predictions of the Antioxidant Capability of Moracin C Isomers
Authors: Parise Angela , De Simone Bruna Clara , Marino Tiziana , Toscano Marirosa , Russo Nino
Published: April 2021

The antioxidant capability of moracin C and iso-moracin C isomers against the OOH free radical was studied by applying density functional theory (DFT) and choosing the M05-2X exchange-correlation functional coupled with the all electron basis set, 6-311++G(d,p), for computations. Different reaction mechanisms [hydrogen atom transfer (HAT), single electron transfer (SET), and radical adduct formation (RAF)] were taken into account when considering water- and lipid-like environments. Rate constants were obtained by applying the conventional transition state theory (TST). The results show that, in water, scavenging activity mainly occurs through a radical addition mechanism for both isomers, while, in the lipid-like environment, the radical addition process is favored for iso-moracin C, while, redox- and non-redox-type reactions can equally occur for moracin C. The values of pKa relative to the deprotonation paths at physiological pH were predicted in aqueous solution.
Evaluating Accuracy of HY-2A/GM-Derived Gravity Data With the Gravity-Geologic Method to Predict Bathymetry
Authors: Wei Zhijie , Guo Jinyun , Zhu Chengcheng , Yuan Jiajia , Chang Xiaotao , Ji Bing
Published: April 2021

For the first time, HY-2A/GM-derived gravity anomalies determined with the least-squares collocation method and ship-borne bathymetry released from the National Centers for Environmental Information (NCEI) are used to predict bathymetry with the gravity-geologic method (GGM) over three test areas located in the South China Sea (105–122°E, 2–26°N). The iterative method is used to determine density contrasts (1.4, 1.5, and 1.6 g/cm3) between seawater and ocean bottom topography, improving the accuracy of GGM bathymetry. The results show that GGM bathymetry is the closest to ship-borne bathymetry at check points, followed by SRTM15+V2.0 model and GEBCO 2020 model. It is found that in a certain range, the relative accuracy of GGM bathymetry tends to improve with the increase of depth. Different geological structures affect the accuracy of GGM bathymetry. In addition, the influences of gravity anomalies and data processing method on GGM bathymetry are analyzed. Our assessment result suggests that GGM can be widely applied to bathymetry prediction and that HY-2A/GM-derived gravity data are feasible with good results in calculating ocean depth.
Acoustic Emission Reveals Multiple Slip Modes on a Frictional Fault
Authors: Ostapchuk Alexey , Morozova Kseniya , Markov Vadim , Pavlov Dmitry , Popov Maxim
Published: April 2021

The spectrum of fault slip modes spans a continuum from fast ruptures to slow slip events. The nucleation of a certain slip mode is governed by the frictional heterogeneity of fault interface and the rheological fault stiffness. There is a mounting evidence that a single fault can host multiple slip modes. In laboratory experiments we study acoustic emission (AE) initiated by a sliding frictional fault and focus our attention on gouge-filled faults hosting multiple slip modes. Deformation experiments were performed on a slider model setup with a precise control of mechanical parameters and monitoring the acoustic signal in the frequency range of 20–80 kHz. We have shown that the cumulative AE energy linearly depends on block displacement. Besides that, there is a high inverse correlation (-0.94) between fault friction andb-valueof frequency-amplitude distribution of AE in the performed experiments. Provided that velocity weakening is specific for the fault interface, the self-organization of a gouge-filled fault at the micro scale is the key parameter that controls the frictional behavior of fault hosting multiple slip modes. Resting on a quantitative categorization of AE waveforms, two AE subpopulations have been distinguished. One of them manifests as AEs with harsh onsets. The second one exhibits a gradual amplitude rise and tremor-like waveforms. A longer duration of the intergrain rupture is specific for the second AE subpopulation. During a laboratory seismic cycle, the first AE subpopulation retains parameters, while the second one exhibits a pronounced cyclic recurrence ofb-value. Theb-valueof the second subpopulation gradually decreases before slip events and recovers after them. Two AE subpopulations, probably, point to the coexistence of two dynamic subsystems. The revealed precursory changes of AE subpopulations are common for the entire spectrum of slip modes. We speculate on the unity of underlying mechanisms of different slip modes.
Self-Efficacy in Early Childhood Education and Care: What Predicts Patterns of Stability and Change in Educator Self-Efficacy?
Authors: Reyhing Yvonne , Perren Sonja
Published: April 2021

Self-efficacy is an important predictor of people’s behaviour and wellbeing. In this longitudinal study we investigated patterns of stability and change in early childhood educator self-efficacy (ESE) in child-centred educational practice and its predictors. Early childhood educators completed a questionnaire twice. Latent profile analysis yielded four profiles: decrease profile (21.2%), increase profile (25.0%), low profile (9.6%), and high profile (44.2%). Profiles were used as the outcome of a multinomial logistic regression analysis. The analyses showed that educators’ experience, number of hours worked per week, and institution are significant predictors for profile membership: educators with less professional experience and fewer working hours per week have a higher probability of being in the low profile. Family-based educators have a higher probability of being in the decrease profile than centre-based educators. The lack of opportunities to increase self-efficacy available to less experienced, part-time educators and family-based working educators are discussed in frame of Bandura’s (1997) sources of self-efficacy. Practical interventions such as coaching and tandem building are proposed to strengthen ESE.
Area Not Geographic Isolation Mediates Biodiversity Responses of Alpine Refugia to Climate Change
Authors: Huxley Jared D. , Spasojevic Marko J.
Published: April 2021

Climate refugia, where local populations of species can persist through periods of unfavorable regional climate, play a key role in the maintenance of regional biodiversity during times of environmental change. However, the ability of refugia to buffer biodiversity change may be mediated by the landscape context of refugial habitats. Here, we examined how plant communities restricted to refugial sky islands of alpine tundra in the Colorado Rockies are changing in response to rapid climate change in the region (increased temperature, declining snowpack, and earlier snow melt-out) and if these biodiversity changes are mediated by the area or geographic isolation of the sky island. We resampled plant communities in 153 plots at seven sky islands distributed across the Colorado Rockies at two time points separated by 12 years (2007/2008–2019/2020) and found changes in taxonomic, phylogenetic, and functional diversity over time. Specifically, we found an increase in species richness, a trend toward increased phylogenetic diversity, a shift toward leaf traits associated with the stress-tolerant end of leaf economics spectrum (e.g., lower specific leaf area, higher leaf dry matter content), and a decrease in the functional dispersion of specific leaf area. Importantly, these changes were partially mediated by refugial area but not by geographic isolation, suggesting that dispersal from nearby areas of tundra does not play a strong role in mediating these changes, while site characteristics associated with a larger area (e.g., environmental heterogeneity, larger community size) may be relatively more important. Taken together, these results suggest that considering the landscape context (area and geographic isolation) of refugia may be critical for prioritizing the conservation of specific refugial sites that provide the most conservation value.
Cryopreservation Preserves Cell-Type Composition and Gene Expression Profiles in Bone Marrow Aspirates From Multiple Myeloma Patients
Authors: Chen Duojiao , Abu Zaid Mohammad I. , Reiter Jill L. , Czader Magdalena , Wang Lin , McGuire Patrick , Xuei Xiaoling , Gao Hongyu , Huang Kun , Abonour Rafat , Walker Brian A. , Liu Yunlong
Published: April 2021

Single-cell RNA sequencing reveals gene expression differences between individual cells and also identifies different cell populations that are present in the bulk starting material. To obtain an accurate assessment of patient samples, single-cell suspensions need to be generated as soon as possible once the tissue or sample has been collected. However, this requirement poses logistical challenges for experimental designs involving multiple samples from the same subject since these samples would ideally be processed at the same time to minimize technical variation in data analysis. Although cryopreservation has been shown to largely preserve the transcriptome, it is unclear whether the freeze-thaw process might alter gene expression profiles in a cell-type specific manner or whether changes in cell-type proportions might also occur. To address these questions in the context of multiple myeloma clinical studies, we performed single-cell RNA sequencing (scRNA-seq) to compare fresh and frozen cells isolated from bone marrow aspirates of six multiple myeloma patients, analyzing both myeloma cells (CD138+) and cells constituting the microenvironment (CD138−). We found that cryopreservation using 90% fetal calf serum and 10% dimethyl sulfoxide resulted in highly consistent gene expression profiles when comparing fresh and frozen samples from the same patient for both CD138+ myeloma cells (R ≥ 0.96) and for CD138– cells (R ≥ 0.9). We also demonstrate that CD138– cell-type proportions showed minimal alterations, which were mainly related to small differences in immune cell subtype sensitivity to the freeze-thaw procedures. Therefore, when processing fresh multiple myeloma samples is not feasible, cryopreservation is a useful option in single-cell profiling studies.
miRNAs Alter T Helper 17 Cell Fate in the Pathogenesis of Autoimmune Diseases
Authors: Huang Junxia , Xu Xinzhi , Yang Ji
Published: April 2021

T helper 17 (Th17) cells are characterized by the secretion of the IL-17 cytokine and are essential for the immune response against bacterial and fungal infections. Despite the beneficial roles of Th17 cells, unrestrained IL-17 production can contribute to immunopathology and inflammatory autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Although these diverse outcomes are directed by the activation of Th17 cells, the regulation of Th17 cells is incompletely understood. The discovery that microRNAs (miRNAs) are involved in the regulation of Th17 cell differentiation and function has greatly improved our understanding of Th17 cells in immune response and disease. Here, we provide an overview of the biogenesis and function of miRNA and summarize the role of miRNAs in Th17 cell differentiation and function. Finally, we focus on recent advances in miRNA-mediated dysregulation of Th17 cell fate in autoimmune diseases.
Clinical and Immunological Factors That Distinguish COVID-19 From Pandemic Influenza A(H1N1)
Authors: Choreño-Parra José Alberto , Jiménez-Álvarez Luis Armando , Cruz-Lagunas Alfredo , Rodríguez-Reyna Tatiana Sofía , Ramírez-Martínez Gustavo , Sandoval-Vega Montserrat , Hernández-García Diana Lizzeth , Choreño-Parra Eduardo M. , Balderas-Martínez Yalbi I. , Martinez-Sánchez Mariana Esther , Márquez-García Eduardo , Sciutto Edda , Moreno-Rodríguez José , Barreto-Rodríguez José Omar , Vázquez-Rojas Hazel , Centeno-Sáenz Gustavo Iván , Alvarado-Peña Néstor , Salinas-Lara Citlaltepetl , Sánchez-Garibay Carlos , Galeana-Cadena David , Hernández Gabriela , Mendoza-Milla Criselda , Domínguez Andrea , Granados Julio , Mena-Hernández Lula , Pérez-Buenfil Luis Ángel , Domínguez-Cheritt Guillermo , Cabello-Gutiérrez Carlos , Luna-Rivero Cesar , Salas-Hernández Jorge , Santillán-Doherty Patricio , Regalado Justino , Hernández-Martínez Angélica , Orozco Lorena , Ávila-Moreno Federico , García-Latorre Ethel A. , Hernández-Cárdenas Carmen M. , Khader Shabaana A. , Zlotnik Albert , Zúñiga Joaquín
Published: April 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.
Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
Authors: Dasilva Gabriel , Lois Salomé , Méndez Lucía , Miralles-Pérez Bernat , Romeu Marta , Ramos-Romero Sara , Torres Josep L. , Medina Isabel
Published: April 2021

Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.
Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders
Authors: Sampah Maame Efua S. , Hackam David J.
Published: April 2021

Prior to birth, the neonate has limited exposure to pathogens. The transition from the intra-uterine to the postnatal environment initiates a series of complex interactions between the newborn host and a variety of potential pathogens that persist over the first few weeks of life. This transition is particularly complex in the case of the premature and very low birth weight infant, who may be susceptible to many disorders as a result of an immature and underdeveloped immune system. Chief amongst these disorders is necrotizing enterocolitis (NEC), an acute inflammatory disorder that leads to necrosis of the intestine, and which can affect multiple systems and have the potential to result in long term effects if the infant is to survive. Here, we examine what is known about the interplay of the immune system with the maternal uterine environment, microbes, nutritional and other factors in the pathogenesis of neonatal pathologies such as NEC, while also taking into consideration the effects on the long-term health of affected children.
Small Molecule Cyclotriazadisulfonamide Abrogates the Upregulation of the Human Receptors CD4 and 4-1BB and Suppresses In Vitro Activation and Proliferation of T Lymphocytes
Authors: Claeys Elisa , Pauwels Eva , Humblet-Baron Stephanie , Provinciael Becky , Schols Dominique , Waer Mark , Sprangers Ben , Vermeire Kurt
Published: April 2021

The small molecule cyclotriazadisulfonamide (CADA) down-modulates the human CD4 receptor, an important factor in T cell activation. Here, we addressed the immunosuppressive potential of CADA using different activation models. CADA inhibited lymphocyte proliferation with low cellular toxicity in a mixed lymphocyte reaction, and when human PBMCs were stimulated with CD3/CD28 beads, phytohemagglutinin or anti-CD3 antibodies. The immunosuppressive effect of CADA involved both CD4+and CD8+T cells but was, surprisingly, most prominent in the CD8+T cell subpopulation where it inhibited cell-mediated lympholysis. Immunosuppression by CADA was characterized by suppressed secretion of various cytokines, and reduced CD25, phosphoSTAT5 and CTPS-1 levels. We discovered a direct down-modulatory effect of CADA on 4-1BB (CD137) expression, a survival factor for activated CD8+T cells. More specifically, CADA blocked 4‑1BB protein biosynthesis by inhibition of its co-translational translocation into the ER in a signal peptide-dependent way. Taken together, this study demonstrates that CADA, as potent down-modulator of human CD4 and 4‑1BB receptor, has promising immunomodulatory characteristics. This would open up new avenues toward chemotherapeutics that act as selective protein down-modulators to treat various human immunological disorders.
Case Report: Leishmania and HIV Co-Diagnosis: How to Understand Medical History?
Authors: Dujardin Arthur , de La Blanchardière Arnaud , Dina Julia , Stefic Karl , Ravel Christophe , Bonhomme Julie , Verdon Renaud , Fournier Anna Lucie
Published: April 2021

We report a case of a severe visceral leishmaniasis revealing an HIV-1 infection presenting as an acute primary infection. A young French man living in Paris with history of unprotected sex with a recent male partner and recent travel in Greece was admitted in our Infectious Diseases Department, presenting with acute febrile psychotic disorder, and positive HIV-1 serology with high viral load, very low CD4+ T-cells count and a western blot pattern suggesting an acute infection. The psychotic disorder was finally related to hemophagocytic lymphohistiocytosis diagnosed on bone marrow aspiration, supposedly secondary to HIV acute primary infection. The progressive worsening of pancytopenia despite antiretroviral treatment and the persistence of fever, chills and sweat led to the diagnosis of visceral leishmaniasis through bone marrow biopsy and leishmanial serology. He was treated with intravenous liposomal amphotericin B with quick improvement. We discuss the way HIV infection and visceral leishmaniasis may have interact to lead to the clinical presentation of our patient.
Current Challenges for IDO2 as Target in Cancer Immunotherapy
Authors: Mondanelli Giada , Mandarano Martina , Belladonna Maria Laura , Suvieri Chiara , Pelliccia Cristina , Bellezza Guido , Sidoni Angelo , Carvalho Agostinho , Grohmann Ursula , Volpi Claudia
Published: April 2021

Immune checkpoint inhibitors have revolutionized the clinical approach of untreatable tumors and brought a breath of fresh air in cancer immunotherapy. However, the therapeutic effects of these drugs only cover a minority of patients and alternative immunotherapeutic targets are required. Metabolism of l-tryptophan (Trp) via the kynurenine pathway represents an important immune checkpoint mechanism that controls adaptive immunity and dampens exaggerated inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the enzyme catalyzing the first, rate–limiting step of the pathway, is expressed in several human tumors and IDO1 catalytic inhibitors have reached phase III clinical trials, unfortunately with disappointing results. Although much less studied, the IDO1 paralog IDO2 may represent a valid alternative as drug target in cancer immunotherapy. Accumulating evidence indicates that IDO2 is much less effective than IDO1 in metabolizing Trp and its functions are rather the consequence of interaction with other, still undefined proteins that may vary in distinct inflammatory and neoplastic contexts. As a matter of fact, the expression of IDO2 gene variants is protective in PDAC but increases the risk of developing tumor in NSCLC patients. Therefore, the definition of the IDO2 interactome and function in distinct neoplasia may open innovative avenues of therapeutic interventions.
The Occurrence and Distribution of Benthic Foraminifera in Tropical Waters Along the Strait of Malacca
Authors: Minhat Fatin Izzati , Ghandhi Suresh M. , Ahzan Nurul Syahirah Mohd , Haq Norizmaira Abdul , Manaf Omar Abdul Rahman Abdul , Sabohi Shinazamreena Mhd , Lee Lee Hin , Akhir Mohd Fadzil , Abdullah Maizah Mohd
Published: April 2021

Foraminifera are shelled single-celled protists that are found in all marine environments. Benthic foraminifera either live in sediments or attach to surfaces on the seafloor. Understanding the distribution and ecological response of benthic foraminifera is crucial, as they can indicate past and current ocean conditions. However, the benthic foraminifera distribution along the busy Strait of Malacca, which connects the Indian Ocean (north) to the Java Sea (south), is undersampled. In this study, we collected 24 surface samples from the northern Strait of Malacca to understand the distribution of foraminifera assemblages in shallow tropical waters. A total of 49 species of benthic foraminifera were identified. Calcareous hyaline species dominated the assemblages, with an extremely low occurrence of calcareous porcelaneous species. The common calcareous hyaline taxa were Asterorotalia pulchella, Pseudorotalia schroeteriana, Discorbinella bertheloti, Ammonia tepida, and Heterolepa praecincta. Cluster analysis categorised the foraminiferal assemblages into three major groups. The first cluster (Group A) consisted of a more diverse assemblage of hyaline and agglutinated species that inhabited a mean water depth of 45 m. The second cluster represented a population that inhabited deeper water environments (average water depth of 59 m). Finally, the third cluster (Group C) consisted of a foraminifera assemblage that inhabited shallow coastal environments (average depth of 22 m) with higher organic matter enrichment. The multivariate canonical correspondence analysis (CCA) showed that the foraminiferal assemblages reflected the shallow to deep water transition in the Malacca Strait. Water depth, which defines the depositional environment, had a greater influence on foraminifera distribution here than organic matter and salinity.
Ammonia Toxicity Induces Oxidative Stress, Inflammatory Response and Apoptosis in Hybrid Grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu)
Authors: Yan Xiaobo , Chen Yu , Dong Xiaohui , Tan Beiping , Liu Hao , Zhang Shuang , Chi Shuyan , Yang Qihui , Liu Hongyu , Yang Yuanzhi
Published: April 2021

To study the effects of acute ammonia stress on the poisoning reaction of the hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu), 300 healthy grouper juveniles with an initial body weight of 51.4 ± 2.57 g were selected for an acute ammonia stress experiment using a half-lethal concentration of ammonia for 24, 48, 72, and 96 h with triplicate. The results show that (1) The half-lethal concentrations of ammonia for a hybrid grouper were 39.5 mg/L for 24 h, 27.3 mg/L for 48 h, 26.5 mg/L for 72 h, and 25.0 mg/L for 96 h, and the safe concentration was 2.50 mg/L. (2) The biochemical indices of the serum and livers of the groupers fluctuated under acute ammonia stress (P < 0.05), and the contents of serum cortisol and lactate reached the maximum value in 72 h (P < 0.05). (3) 24 h ammonia stress increased the activities of alkaline phosphatase, acid phosphatase, catalase, glutathione peroxidase, superoxide dismutase, lysozyme, and the content of immunoglobulin M in the liver (P < 0.05). Meanwhile, all ammonia-stressed fish groups had an increased amount of malondialdehyde in the liver (P < 0.05). (4) The ammonia poisoning caused significantly up-regulation of antioxidant genes, inflammatory cytokines, and apoptosis genes (P < 0.05), and the expression of inflammatory cytokines and apoptosis genes were the highest in 24 h ammonia stress group. (5) The ammonia content in the water changed the abundance and evenness of intestinal microbes in grouper, mainly in that ammonia stress significantly increased the relative abundance of fusobacteria, but significantly decreased the relative abundance of gemmatimonadetes (P < 0.05). It was speculated that apoptosis induced by ammonia poisoning in grouper may be related to oxidative stress and the activation of inflammatory factors, and excessive inflammatory stress may be one of the causes of ammonia poisoning in the hybrid grouper.
Not as Bad as It Seems? A Literature Review on the Case of Microplastic Uptake in Fish
Authors: Müller Carolin
Published: April 2021

Within the past decade, microplastic (MP) particles (<5 mm in size) became the focus of both scientific and public attention, on one hand due to their cumulative industrial application and global presence, on the other hand due to their size range allowing the interaction with organisms at the base of the marine food web. Along with the growing evidence of their ubiquitous distribution, the ingestion of MP fibers and fragments has been verified for a variety of marine biota, with fish species being among the group of organisms most intensively studied both in the laboratory and in the field. While the gross of scientific literature focuses on the quantification and chemical characterization of MP in the gastrointestinal tract of fish, in-depth investigations on the impacts or a contextualization of ingestion are rarely accomplished. Yet, the constant media-coverage and omnipresence of the topic present a (threat) scenario among civil society which might lack a solid scientific foundation. This review, therefore, analyses the scientific output of 90 field studies covering 487 different fish taxa with due regard to explanatory variables for MP ingestion. Additionally, it highlights persistent knowledge gaps in relation to the examination of in-situ ingestion effects and proposes measures how to approach them in future research initiatives. Moreover, the potential existence of a publication bias and a consequent distortion of the perception of the topic is evaluated.
Advantages and Limitations of Surface Analysis Techniques on Plasma-Treated Arabidopsis thaliana Seeds
Authors: Waskow Alexandra , Howling Alan , Furno Ivo
Published: April 2021

Surface characterization of plasma-treated seeds has made significant progress over the last decade. Most papers in the literature use scanning electron microscopy (SEM) and contact angle goniometry to investigate surface modifications. However, very few papers address the chemical modifications to the seed coat after plasma treatment. Here, a summary of the methods used to analyze plasma-treated seeds is presented, such as SEM, contact angle goniometry, energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The results obtained on Arabidopsis thaliana Col-0 seeds and the limitations of these techniques are discussed. An experiment was designed in order to compare the relative advantages and limitations of these surface analysis techniques by investigating the separate effects of plasma, heat, and ozone on A. thaliana seeds.
Investigation of Structure-Property-Boiling Enhancement Mechanisms of Copper/Graphene Nanoplatelets Coatings
Authors: Rishi Aniket M. , Rozati Seyed Alireza , Trybus Carole , Kandlikar Satish G. , Gupta Anju
Published: April 2021

In this work, we present an exceptionally high heat transfer coefficient (HTC) and critical heat flux (CHF) achieved by graphene nanoplatelets (GNPs) and copper composite coatings with tunable surface properties. These coatings were created by a combination of powder metallurgy and manufacturing processes including ball milling, sintering, electrodeposition, and salt-patterning. We demonstrated correlations between various coating processes, resultant surface morphologies, properties, and improved boiling mechanism. Electrodeposition of GNP and copper particles led to formation of tall ridge-like structures and valleys to contain the boiling fluid in between. Higher CHF achieved for these coatings was attributed to the microlayer evaporation. It was observed that ball milling of GNP and copper particles prior to their sinter-coating enhanced their surface roughness that resulted in very high HTC, nearly 5.4 times higher than plain copper surfaces. Additional salt-patterning along with sinter-coating yielded interconnected porous networks with high nucleating activity that rendered record-breaking HTC of 1,314°kW/m2-°C. Combination of these coating processes can be adopted to tailor the surfaces and achieve better boiling performance. Novel techniques developed in this work can be applied to a variety of thermal engineering applications.
Biosolids as a Source of Antibiotic Resistance Plasmids for Commensal and Pathogenic Bacteria
Authors: Law Aaron , Solano Olubunmi , Brown Celeste J. , Hunter Samuel S. , Fagnan Matt , Top Eva M. , Stalder Thibault
Published: April 2021

Antibiotic resistance (AR) is a threat to modern medicine, and plasmids are driving the global spread of AR by horizontal gene transfer across microbiomes and environments. Determining the mobile resistome responsible for this spread of AR among environments is essential in our efforts to attenuate the current crisis. Biosolids are a wastewater treatment plant (WWTP) byproduct used globally as fertilizer in agriculture. Here, we investigated the mobile resistome of biosolids that are used as fertilizer. This was done by capturing resistance plasmids that can transfer to human pathogens and commensal bacteria. We used a higher-throughput version of the exogenous plasmid isolation approach by mixing several ESKAPE pathogens and a commensal Escherichia coli with biosolids and screening for newly acquired resistance to about 10 antibiotics in these strains. Six unique resistance plasmids transferred to Salmonella typhimurium, Klebsiella aerogenes, and E. coli. All the plasmids were self-transferable and carried 3–6 antibiotic resistance genes (ARG) conferring resistance to 2–4 antibiotic classes. These plasmids-borne resistance genes were further embedded in genetic elements promoting intracellular recombination (i.e., transposons or class 1 integrons). The plasmids belonged to the broad-host-range plasmid (BHR) groups IncP-1 or PromA. Several of them were persistent in their new hosts when grown in the absence of antibiotics, suggesting that the newly acquired drug resistance traits would be sustained over time. This study highlights the role of BHRs in the spread of ARG between environmental bacteria and human pathogens and commensals, where they may persist. The work further emphasizes biosolids as potential vehicles of highly mobile plasmid-borne antibiotic resistance genes.
Elevated Atmospheric CO2 and Nitrogen Fertilization Affect the Abundance and Community Structure of Rice Root-Associated Nitrogen-Fixing Bacteria
Authors: Liu Jumei , Han Jingjing , Zhu Chunwu , Cao Weiwei , Luo Ying , Zhang Meng , Zhang Shaohua , Jia Zhongjun , Yu Ruihong , Zhao Ji , Bao Zhihua
Published: April 2021

Elevated atmospheric CO2 (eCO2) results in plant growth and N limitation, yet how root-associated nitrogen-fixing bacterial communities respond to increasing atmospheric CO2 and nitrogen fertilization (eN) during the growth stages of rice is unclear. Using the nifH gene as a molecular marker, we studied the combined effect of eCO2 and eN on the diazotrophic community and abundance at two growth stages in rice (tillering, TI and heading, HI). Quantitative polymerase chain reaction (qPCR) showed that eN had no obvious effect on nifH abundance in rice roots under either ambient CO2 (aCO2) or eCO2 treatment at the TI stage; in contrast, at the HI, nifH copy numbers were increased under eCO2 and decreased under aCO2. For rhizosphere soils, eN significantly reduced the abundance of nifH under both aCO2 and eCO2 treatment at the HI stage. Elevated CO2 significantly increased the nifH abundance in rice roots and rhizosphere soils with nitrogen fertilization, but had no obvious effect without N addition at the HI stage. There was a significant interaction [CO2 × N fertilization] effect on nifH abundance in root zone at the HI stage. In addition, the nifH copy numbers in rice roots were significantly higher at the HI stage than at the TI stage. Sequencing analysis indicated that the root-associated diazotrophic community structure tended to cluster according to the nitrogen fertilization treatment and that Rhizobiales were the dominant diazotrophs in all root samples at the HI stage. Additionally, nitrogen fertilization significantly increased the relative abundance of Methylosinus (Methylocystaceae) under eCO2 treatment, but significantly decreased the relative abundance of Rhizobium (Rhizobiaceae) under aCO2 treatment. Overall, the combined effect of eN and eCO2 stimulates root-associated diazotrophic methane-oxidizing bacteria while inhibits heterotrophic diazotrophs.
An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility
Authors: Coppola Guglielmo Attilio , Onsea Jolien , Moriarty T. Fintan , Nehrbass Dirk , Constant Caroline , Zeiter Stephan , Aktan Merve Kübra , Braem Annabel , Van der Eycken Erik V. , Steenackers Hans P. , Metsemakers Willem-Jan
Published: April 2021

Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the bacteria from the host immune system and most common antibiotic drugs, which renders them essentially antibiotic-tolerant. There is an urgent clinical need for novel strategies to prevent these serious infections that do not involve conventional antibiotics. Recently, a novel antibiofilm coating for titanium surfaces was developed based on 5-(4-bromophenyl)-N-cyclopentyl-1-octyl-1H-imidazol-2-amine as an active biofilm inhibitor. In the current study we present an optimized coating protocol that allowed for a 5-fold higher load of this active compound, whilst shortening the manufacturing process. When applied to titanium disks, the newly optimized coating was resilient to the most common sterilization procedures and it induced a 1 log reduction in biofilm cells of a clinical Staphylococcus aureus isolate (JAR060131) in vitro, without affecting the planktonic phase. Moreover, the antibiofilm effect of the coating in combination with the antibiotic cefuroxime was higher than cefuroxime treatment alone. Furthermore, the coating was successfully applied to a human-scale fracture fixation device resulting in a loading that was comparable to the titanium disk model. Finally, an in vivo biocompatibility and healing study in a rabbit osteotomy model indicated that these coated implants did not negatively affect fracture healing or osteointegration. These findings put our technology one step closer to clinical trials, confirming its potential in fighting orthopedic infections without compromising healing.
Co-infection of H9N2 Influenza A Virus and Escherichia coli in a BALB/c Mouse Model Aggravates Lung Injury by Synergistic Effects
Authors: Wang Song , Jiang Ning , Shi Wenhao , Yin Hang , Chi Xiaojuan , Xie Yanhui , Hu Jingyun , Zhang Yanwei , Li Huangping , Chen Ji-Long
Published: April 2021

Pathogens that cause respiratory diseases in poultry are highly diversified, and co-infections with multiple pathogens are prevalent. The H9N2 strain of avian influenza virus (AIV) and Escherichia coli (E. coli) are common poultry pathogens that limit the development of the poultry industry. This study aimed to clarify the interaction between these two pathogens and their pathogenic mechanism using a mouse model. Co-infection with H9N2 AIV and E. coli significantly increased the mortality rate of mice compared to single viral or bacterial infections. It also led to the development of more severe lung lesions compared to single viral or bacterial infections. Co-infection further causes a storm of cytokines, which aggravates the host’s disease by dysregulating the JAK/STAT/SOCS and ERK1/2 pathways. Moreover, co-infection mutually benefited the virus and the bacteria by increasing their pathogen loads. Importantly, nitric oxide synthase 2 (NOS2) expression was also significantly enhanced by the co-infection. It played a key role in the rapid proliferation of E. coli in the presence of the co-infecting H9N2 virus. Therefore, our study underscores the role of NOS2 as a determinant for bacteria growth and illustrates its importance as an additional mechanism that enhances influenza virus-bacteria synergy. It further provides a scientific basis for investigating the synergistic infection mechanism between viruses and bacteria.