bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGEMBANGAN E-MODULE MENGGUNAKAN APLIKASI 3D PAGEFLIP PROFESSIONAL PADA POKOK BAHASAN ASAM DAN BASA (IN PRESS)
Authors: Oktavia Sindy , Haryati Sri , Erviyenni Erviyenni
Published: January 2021

Pembelajaran abad 21 identik dengan penggunaan teknologi dalam proses pembelajaran sehingga pembelajaran menjadi inovatif, menarik, dan berkualitas. Tujuan penelitian ini yaitu mengembangkan e-module menggunakan aplikasi 3D Pageflip Professional pada pokok bahasan asam dan basa dengan kategori valid berdasarkan aspek substansi isi, desain pembelajaran, komunikasi visual, dan pemanfaatan software. Prosedur pengembangan yang digunakan dalam penelitian ini yaitu merujuk pada model pengembangan ADDIE (Analyze, Design, Develop, Implementation, Evaluate). Instrumen penelitian berupa lembar validasi yang dinilai oleh dua orang ahli materi dan dua orang ahli media. Hasil yang diperoleh dari analisis data validasi pada aspek substansi isi, desain pembelajaran, komunikasi visual dan pemanfaatan software berturut-turut sebesar 94,44%, 94,917%, 94,318%, dan 95,83% dengan kriteria valid. E-module yang telah memperoleh kriteria valid menurut validator diuji respon kepada tiga orang guru bidang studi kimia dan 20 orang peserta didik. Hasil persentase respon peserta didik sebesar 92,596% dengan kriteria sangat baik, dan hasil persentase respon guru sebesar 95,58%. Kesimpulan yang diperoleh dari hasil analisis data tersebut bahwa dihasilkan e-module menggunakan aplikasi 3D Pageflip Professional yang valid dan dapat digunakan dalam proses pembelajaran kimia tingkat SMA pada pokok bahasan Asam dan basa.
Comportamiento frágil de las armaduras corroídas
Authors: Sánchez Montero Javier , Rebolledo Ramos Nuria , Torres Martín Julio E.
Published: January 2021

La corrosión de las armaduras es una de las principales razones de la reducción de la durabilidad de las estructuras de hormigón armado. Por otra parte, existen diversos mecanismos de corrosión que dan lugar a la generación de diferentes defectos con geometrías diferentes.

El presente estudio se centra en evaluar el comportamiento mecánico de armaduras con diferentes tipos de defectos, desde corrosión generalizada, por picaduras hasta corrosión bajo tensión y fragilización por hidrógeno. Los resultados obtenidos muestran que la resistencia de los aceros no depende únicamente de la pérdida de material, sino que es muy importante evaluar la geometría de los defectos. Estos resultados permiten explicar la variación en el comportamiento mecánico de armaduras corroídas por diferentes métodos.
Refuerzo externo a cortante en vigas de hormigón mediante aleaciones con memoria de forma en base hierro: de la prueba de concepto a la escala real
Authors: Cladera Bohigas Antoni , Montoya Coronado Luis Alberto , Ruiz Pinilla Joaquín Guillermo , Ribas González Carlos Rodrigo
Published: January 2021

Las barras corrugadas y los flejes de aleación con memoria de forma en base hierro (Fe-SMA, de su denominación en inglés) son ya una realidad en el mercado europeo de la construcción y, de hecho, ya son varios los proyectos reales en los que estos elementos se han utilizado para el refuerzo estructural a flexión. En esta comunicación se presentará la tecnología desarrollada por los autores para el refuerzo externo a cortante mediante la utilización de flejes de Fe-SMA.

Es preciso destacar que estas aleaciones tienen una característica de gran interés para la ingeniería estructural: son capaces de recordar una forma e intentar volver a ella tras su calentamiento y posterior enfriamiento hasta temperatura ambiente. Este proceso también es conocido como activación. En el caso de utilizar estos materiales como refuerzo externo, los flejes o barras corrugadas se fijan a la estructura, por lo que cuando se produce la activación, las deformaciones se encuentran impedidas, apareciendo tensiones de compresión y/o confinamiento en el elemento estructural y de tracción en el elemento de refuerzo. De esta forma es posible postesar la estructura sin necesidad de utilizar vainas, gatos hidráulicos o cuñas de anclaje.

En esta comunicación se describirán dos campañas experimentales de refuerzo externo a cortante: la primera de ellas llevada a cabo como prueba de concepto en vigas de hormigón a pequeña escala, y la segunda en vigas a escala real con sección en T. Además se comentarán las dificultades encontradas y los resultados obtenidos, a nivel material y estructural, que confirman la gran potencialidad que estos materiales tienen en ingeniería estructural.
Nuevo viaducto sobre el río Júcar en Cullera: Lanzamiento mediante SPMTs
Authors: Sopeña Corvinos Luis , Álvarez Andrés Juan Jesús , Lucas Serrano Conchita , Rico Rubio Ricardo , Valor González Sara , Misas Muñoz Carlos
Published: January 2021

El viaducto sobre el Júcar es un puente mixto de 216 m de longitud y 29 m de ancho de plataforma cuyo vano principal es un arco de tablero inferior de 90 m de luz, que en otra comunicación se describe con detalle. Descartada la opción de montaje con grúas por la dificultad que tal maniobra entrañaba, el proceso de ejecución elegido fue un lanzamiento poco convencional mediante el uso de carretones autopropulsados o SPMTs (Self Propelled Modular Transport). Debido a las condiciones particulares del lanzamiento, este método resultó ventajoso respecto a los empujes convencionales (ahorro en acero de refuerzo, diagonales provisionales, disminución voladizo de construcción).
Diseño y construcción del Nuevo Puente de Espartxo sobre el río Urumea, San Sebastián
Authors: Capellán Miguel Guillermo , García Pérez Marianela , Sacristán Montesinos Miguel , Berrazueta Sánchez de Vega José D. , Godoy Ansótegui Alejandro
Published: January 2021

El Nuevo Puente de Espartxo, actualmente en construcción, sustituirá al ya deteriorado Espartxo Zubia, de solo 6,60 m de ancho, que ha quedado obsoleto por su reducida anchura, la ausencia de aceras y carril bici, y su baja cota que podría generar problemas hidráulicos. La actuación forma parte del conjunto de obras de urbanización del área LM.06 de Txomin-Enea, situado entre los barrios de Loiola y Martutene, promovidas por el Ayuntamiento de San Sebastián.

El nuevo puente tiene una longitud de 59.4 m entre apoyos de estribos, repartidos en dos vanos metálicos de 42 m y 17.4 m, con una única pila singular situada en margen izquierda, formada por dos brazos en V de hormigón con superficies regladas alabeadas y núcleo central metálico, lo cual mejora el comportamiento hidráulico y disminuye el coste en cimentaciones.

La sección transversal del puente alcanza una sección útil de 18,30 m, con calzada central de 7 m para dos carriles de circulación de 3,20 m, una acera en voladizo de 4 m aguas abajo, y un voladizo de 5,50 m aguas arriba, formado por una acera exterior de 3 m y un carril bici de 2,50 m.

La planta del puente es su característica más singular, al abrirse los voladizos de aceras en el vano lateral de 17,40 m, hasta independizarse del núcleo central del tablero para formar sendas pasarelas laterales. El núcleo central del tablero, de 8,80 m de ancho, incluye la calzada y la estructura principal del mismo, y se ejecuta en primer lugar. Los nervios de borde metálicos de los laterales, conforman las barreras entre calzada y aceras. Esta configuración permite respetar el gálibo hidráulico necesario reduciendo el canto bajo rasante y también el canto aparente de tablero, con lo que el resultado es una estructura muy esbelta.
Challenges and Current Status of the Biological Treatment of PFAS-Contaminated Soils
Authors: Shahsavari Esmaeil , Rouch Duncan , Khudur Leadin S. , Thomas Duncan , Aburto-Medina Arturo , Ball Andrew S.
Published: January 2021

Per- and polyfluoroalkyl substances (PFAS) are Synthetic Organic Compounds (SOCs) which are of current concern as they are linked to a myriad of adverse health effects in mammals. They can be found in drinking water, rivers, groundwater, wastewater, household dust, and soils. In this review, the current challenge and status of bioremediation of PFAs in soils was examined. While several technologies to remove PFAS from soil have been developed, including adsorption, filtration, thermal treatment, chemical oxidation/reduction and soil washing, these methods are expensive, impractical for in situ treatment, use high pressures and temperatures, with most resulting in toxic waste. Biodegradation has the potential to form the basis of a cost-effective, large scale in situ remediation strategy for PFAS removal from soils. Both fungal and bacterial strains have been isolated that are capable of degrading PFAS; however, to date, information regarding the mechanisms of degradation of PFAS is limited. Through the application of new technologies in microbial ecology, such as stable isotope probing, metagenomics, transcriptomics, and metabolomics there is the potential to examine and identify the biodegradation of PFAS, a process which will underpin the development of any robust PFAS bioremediation technology.
Enhanced Osseointegration by the Hierarchical Micro-Nano Topography on Selective Laser Melting Ti-6Al-4V Dental Implants
Authors: Shu Tianyu , Zhang Yuchen , Sun Guo , Pan Yang , He Gang , Cheng Yilong , Li Ang , Pei Dandan
Published: January 2021

Currently, selective laser melting (SLM) has been thriving in implant dentistry for on-demand fabricating dental implants. Based on the coarse microtopography of SLM titanium surfaces, constructing nanostructure to form the hierarchical micro-nano topography is effective in enhancing osseointegration. Given that current nanomodification techniques of SLM implants, such as anodization and hydrothermal treatment, are facing the inadequacy in costly specific apparatus and reagents, there has been no recognized nanomodified SLM dental implants. The present study aimed to construct hierarchical micro-nano topography on self-made SLM dental implants by a simple and safe inorganic chemical oxidation, and to evaluate its contribution on osteoblastic cells bioactivity and osseointegration. The surface chemical and physical parameters were characterized by FE-SEM, EDS, profilometer, AFM, and contact angle meter. The alteration on bioactivity of MG-63 human osteoblastic cells were detected by qRT-PCR. Then the osseointegration was assessed by implanting implants on the femur condyle of New Zealand Rabbits. The hierarchical micro-nano topography was constituted by the microrough surface of SLM implants and nanoneedles (diameter: 20∼50 nm, height: 150∼250 nm), after nanomodifying SLM implants in 30% hydrogen peroxide and 30% hydrochloride acid (volume ratio 1:2.5) at room temperature for 36 h. Low chemical impurities content and high hydrophilicity were observed in the nanomodified group. Cell experiments on the nanomodified group showed higher expression of mitophagy related gene (PINK1, PARKIN, LC3B, and LAMP1) at 5 days and higher expression of osteogenesis related gene (Runx2 and OCN) at 14 days. In the early stage of bone formation, the nanomodified SLM implants demonstrated higher bone-to-implant contact. Intriguingly, the initial bone-to-implant contact of nanomodified SLM implants consisted of more mineralized bone with less immature osteoid. After the cessation of bone formation, the bone-to-implant contact of nanomodified SLM implants was equal to untreated SLM implants and marketable TixOs implants. The overall findings indicated that the inorganic chemical oxidized hierarchical micro-nano topography could enhance the bioactivity of osteoblastic cells, and consequently promote the peri-implant bone formation and mineralization of SLM dental implants. This study sheds some light on improvements in additive manufactured dental implants.
Tmc Reliance Is Biased by the Hair Cell Subtype and Position Within the Ear
Authors: Zhu Shaoyuan , Chen Zongwei , Wang Haoming , McDermott Brian M.
Published: January 2021

Hair cells are heterogenous, enabling varied roles in sensory systems. An emerging hypothesis is that the transmembrane channel-like (Tmc) proteins of the hair cell’s mechanotransduction apparatus vary within and between organs to permit encoding of different mechanical stimuli. Five anatomical variables that may coincide with different Tmc use by a hair cell within the ear are the containing organ, cell morphology, cell position within an organ, axis of best sensitivity for the cell, and the hair bundle’s orientation within this axis. Here, we test this hypothesis in the organs of the zebrafish ear using a suite of genetic mutations. Transgenesis and quantitative measurements demonstrate two morphologically distinct hair cell types in the central thickness of a vestibular organ, the lateral crista: short and tall. In contrast to what has been observed, we find that tall hair cells that lack Tmc1 generally have substantial reductions in mechanosensitivity. In short hair cells that lack Tmc2 isoforms, mechanotransduction is largely abated. However, hair cell Tmc dependencies are not absolute, and an exceptional class of short hair cell that depends on Tmc1 is present, termed a short hair cell erratic. To further test anatomical variables that may influence Tmc use, we map Tmc1 function in the saccule of mutant larvae that depend just on this Tmc protein to hear. We demonstrate that hair cells that use Tmc1 are found in the posterior region of the saccule, within a single axis of best sensitivity, and hair bundles with opposite orientations retain function. Overall, we determine that Tmc reliance in the ear is dependent on the organ, subtype of hair cell, position within the ear, and axis of best sensitivity.
Identification of a Prognostic Immune Signature for Esophageal Squamous Cell Carcinoma to Predict Survival and Inflammatory Landscapes
Authors: Zhang Chaoqi , Luo Yuejun , Zhang Zhen , Zhang Zhihui , Zhang Guochao , Wang Feng , Che Yun , Fang Lingling , Zhang Yi , Sun Nan , He Jie
Published: January 2021

Immunotherapy has achieved success in the treatment of esophageal squamous cell carcinoma (ESCC). However, studies concerning immune phenotypes within the ESCC microenvironment and their relationship with prognostic outcomes are limited. We constructed and validated an individual immune-related risk signature for patients with ESCC. We collected 196 ESCC cases, including 119 samples from our previous public data (GSE53624) to use as a training set and an independent cohort with 77 quantitative real-time polymerase chain reaction (qRT-PCR) data, which we used for validation. Head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC) cohorts were also collected for validation. A least absolute shrinkage and selection operator (LASSO) model and a stepwise Cox proportional hazards regression model were used to construct the immune-specific signature. The potential mechanism and inflammatory landscapes of the signature were explored using bioinformatics and immunofluorescence assay methods. This signature predicted different prognoses in clinical subgroups and the independent cohort, as well as in patients with HNSCC and LUSC. Further exploration revealed that the signature was associated with specific inflammatory activities (activation of macrophages and T-cell signaling transduction). Additionally, high-risk patients exhibited distinctive immune checkpoints panel and higher regulatory T cell and fibroblast infiltration. This signature served as an independent prognostic factor in ESCC. This was the first applicable immune-related risk signature for ESCC. Our results furnished new hints of immune profiling of ESCC, which may provide some clues to further optimize associated cancer immunotherapies.
Control of T-Cell Activation and Signaling by Amino-Acid Catabolizing Enzymes
Authors: Castellano Flavia , Molinier-Frenkel Valérie
Published: January 2021

Amino acids are essential for protein synthesis, epigenetic modification through the methylation of histones, and the maintenance of a controlled balance of oxidoreduction via the production of glutathione and are precursors of certain neurotransmitters. T lymphocytes are particularly sensitive to fluctuations in amino acid levels. During evolution, the production of amino-acid catabolizing enzymes by mainly antigen-presenting cells has become a physiological mechanism to control T-cell activation and polarization. The action of these enzymes interferes with TCR and co-stimulation signaling, allowing tuning of the T-cell response. These capacities can be altered in certain pathological conditions, with relevant consequences for the development of disease.
A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior
Authors: Odegaard Katherine E. , Schaal Victoria L. , Clark Alexander R. , Koul Sneh , Sankarasubramanian Jagadesan , Xia Zhiqiu , Mellon Melissa , Uberti Mariano , Liu Yutong , Stothert Andrew , Van Hook Matthew , Wang Hanjun , Guda Chittibabu , Lisco Steven J. , Pendyala Gurudutt , Yelamanchili Sowmya V.
Published: January 2021

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes.

Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (1H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood.

Results:1H-MRS studies revealed significant changes in key brain metabolites in the exposed offspring that were corroborated with changes in synaptic currents. Transcriptomic analysis employing RNA-sequencing identified alterations in the expression of pivotal genes associated with synaptic transmission, neurodevelopment, mood disorders, and addiction in the treatment groups. Furthermore, Von Frey analysis revealed lower pain thresholds in both exposed groups.

Conclusions: Given the increased use of opiates, understanding the persistent developmental effects of these drugs on children will delineate potential risks associated with opiate use beyond the direct effects in pregnant women.
A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes
Authors: Labat-de-Hoz Leticia , Rubio-Ramos Armando , Casares-Arias Javier , Bernabé-Rubio Miguel , Correas Isabel , Alonso Miguel A.
Published: January 2021

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.
Elevated Levels of Oxidative Nucleic Acid Modification Markers in Urine From Gastric Cancer Patients: Quantitative Analysis by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry
Authors: Chen Qin , Hu Yiqiu , Fang Zhihao , Ye Minfeng , Li Jingqing , Zhang Suzhan , Yuan Ying , Guo Cheng
Published: January 2021

Oxidative nucleic acid modifications have attracted increasing attention in recent years since they have been found to be related to a number of diseases including cancer. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG) are the typical markers of oxidative modification of DNA and RNA, respectively, and they are emerging biomarkers for the early detection of diseases. Urine is a favored biofluid for biomarker discovery due to its noninvasiveness to patients. Accurate quantification of these oxidative nucleic acid modifications still has challenges because their amounts in urine are very low and the interferences in urine samples are complicated. Herein, we developed and validated an accurate and robust solid-phase extraction (SPE) coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of these oxidative nucleic acid modifications in human urine. Stable isotope dilution strategy was utilized and the method shows good precision on intraday and interday measurements. Meanwhile, recovery was satisfactory by utilizing the Oasis hydrophilic–lipophilic balance (HLB) cartridge for sample pretreatment at three spiked levels. We successfully quantified urinary 8-OHdG and 8-OHG from 60 gastric cancer patients and 70 healthy controls by using this method. The measured contents of 8-OHdG and 8-OHG in urine from gastric cancer patients are both increased, compared with those in urine from healthy controls, indicating these oxidative nucleic acid modifications could act as potential non-invasive markers for early diagnosis of gastric cancer. Moreover, the present study will stimulate investigations of the effects of oxidative stress and nucleic acid modifications on the initiation and progression of gastric cancer.
Necator americanus Ancylostoma Secreted Protein-2 (Na-ASP-2) Binds an Ascaroside (ascr#3) in Its Fatty Acid Binding Site
Authors: El Atab Ola , Darwiche Rabih , Truax Nathanyal J. , Schneiter Roger , Hull Kenneth G. , Romo Daniel , Asojo Oluwatoyin A.
Published: January 2021

During their infective stages, hookworms release excretory-secretory (E-S) products, small molecules, and proteins to help evade and suppress the host's immune system. Small molecules found in E-S products of mammalian hookworms include nematode derived metabolites like ascarosides, which are composed of the sugar ascarylose linked to a fatty acid side chain. The most abundant proteins found in hookworm E-S products are members of the protein family known as Ancylostoma secreted protein (ASP). In this study, two ascarosides and their fatty acid moieties were synthesized and tested for in vitro binding to Na-ASP-2 using both a ligand competition assay and microscale thermophoresis. The fatty acid moieties of both ascarosides tested and ascr#3, an ascaroside found in rat hookworm E-S products, bind to Na-ASP-2's palmitate binding cavity. These molecules were confirmed to bind to the palmitate but not the sterol binding sites. An ascaroside, oscr#10, which is not found in hookworm E-S products, does not bind to Na-ASP-2. More studies are required to determine the structural basis of ascarosides binding by Na-ASP-2 and to understand the physiological significance of these observations.
A Bridge to Where? Tracing the Bridge Fuel Metaphor in the Canadian Media Sphere
Authors: Chen Sibo
Published: January 2021

This paper examines how Canadian media have discussed the role of natural gas in climate change mitigation from 2016 to 2019. It also explicates different stakeholders' varying stances on the environmental impacts of North America's ongoing “shale gas boom,” as manifested in their conflicting attitudes toward designating unconventional gas as a bridge to a low-carbon future. The data in question consist of 99 articles published by Canadian media sources, all of which included explicit references to either “bridge fuel” or “transition fuel.” Through a qualitative thematic analysis, I found that more than half of the articles adopted the conventional definition of bridge fuel. Meanwhile, there are three less common, yet noteworthy interpretations arising out of the rest of the articles, which conflict with each other in terms of their views on the relationship between unconventional gas and greenhouse gas emissions reduction. Overall, the fact that bridge fuel references only appeared in a fraction of Canadian environmental and energy news reports during the target period suggests the issue's peripheral status in the Canadian media sphere. Given this situation, the paper ends by calling for more knowledge mobilization efforts to raise public awareness of the controversial factors underlying expanding unconventional gas production and consumption.
Brittle Deformation During Eclogitization of Early Paleozoic Blueschist
Authors: Bukała Michał , Barnes Christopher J. , Jeanneret Pauline , Hidas Károly , Mazur Stanisław , Almqvist Bjarne S. G. , Kośmińska Karolina , Klonowska Iwona , Šurka Juraj , Majka Jarosław
Published: January 2021

The Tsäkkok Lens of the Scandinavian Caledonides represents the outermost Baltican margin that was subducted in late Cambrian/Early Ordovician time during closure of the Iapetus Ocean. The lens predominantly consists of metasedimentary rocks hosting eclogite bodies that preserve brittle deformation on the μm-to-m scale. Here, we present a multidisciplinary approach that reveals fracturing related to dehydration and eclogitization of blueschists. Evidence for dehydration is provided by relic glaucophane and polyphase inclusions in garnet consisting of clinozoisite + quartz ± kyanite ± paragonite that are interpreted as lawsonite pseudomorphs. X-Ray chemical mapping of garnet shows a network of microchannels that propagate outward from polyphase inclusions. These microchannels are healed by garnet with elevated Mg relative to the surrounding garnet. Electron backscatter diffraction mapping revealed that Mg-rich microchannels are also delimited by low angle (<3°) boundaries. X-ray computed microtomography demonstrates that some garnet is transected by up to 300 μm wide microfractures that are sealed by omphacite ± quartz ± phengite. Locally, mesofractures sealed either by garnet- or omphacite-dominated veins transect through the eclogites. The interstices within the garnet veins are filled with omphacite + quartz + rutile + glaucophane ± phengite. In contrast, omphacite veins are predominantly composed of omphacite with minor apatite + quartz. Omphacite grains are elongated along [001] crystal axis and are preferably oriented orthogonal to the vein walls, indicating crystallization during fracture dilation. Conventional geothermobarometry using omphacite, phengite and garnet adjacent to fractures, provides pressure-temperature conditions of 2.47 ± 0.32 GPa and 620 ± 60°C for eclogites. The same method applied to a mesoscale garnet vein yields 2.42 ± 0.32 GPa at 635 ± 60°C. Zirconium-in-rutile thermometry applied to the same garnet vein provides a temperature of ∼620°C. Altogether, the microchannels, microfractures and mesofractures represent migration pathways for fluids that were produced during glaucophane and lawsonite breakdown. The microfractures are likely precursors of the mesoscale fractures. These dehydration reactions indicate that high pore-fluid pressure was a crucial factor for fracturing. Brittle failure of the eclogites thus represents a mechanism for fluid-escape in high-pressure conditions. These features may be directly associated with seismic events in a cold subduction regime.
In “Vitro” Lps-Stimulated Sertoli Cells Pre-Loaded With Microparticles: Intracellular Activation Pathways
Authors: Arato Iva , Milardi Domenico , Giovagnoli Stefano , Grande Giuseppe , Bellucci Catia , Lilli Cinzia , Bartoli Sara , Corneli Sara , Mazzone Piera , Calvitti Mario , Baroni Tiziano , Calafiore Riccardo , Mancuso Francesca , Luca Giovanni
Published: January 2021

Sertoli cells (SC) are immune privileged cells with the capacity of modulating the immune response by expressing several immune-regulatory factors. SC have the capacity to respond to external stimuli through innate phagocytic and antibacterial activities. This evidence evoked a potential role of SC as drug carriers and therapeutic agents. Such stimuli drive SC towards a still unknown evolution, the clinical relevance of which as yet remains undisclosed. This study sought to investigate the effects of external stimuli in the form of polymeric microparticles (MP) and bacteria derived endotoxins, such as lipopolysaccharides (LPS), in order to identify the pathways potentially involved in cell phenotype modifications. Compared to single stimulation, when combined, MP and LPS provoked a significant increase in the gene expression of IDO, PD-L1, FAS-L, TLR-3, TLR-4, MHC-II, ICAM-1, TFGβ1, BDF123, BDF129, BDF3 and pEP2C. Western Blotting analysis demonstrated up-regulation of the ERK 1–2 and NF-kB p65 phosphorylation ratios. Our study, showing the exponential increase of these mediators upon combined MP and LPS stimulation, suggests a “switch” of SC function from typical cells of the blood-testicular barrier to nonprofessional tolerogenic antigen-presenting cells. Further studies should target the clinical and technological implications of such stimuli-induced SC transformation.
microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression
Authors: Fitzsimons Stephen , Oggero Silvia , Bruen Robyn , McCarthy Cathal , Strowitzki Moritz J. , Mahon Niall G. , Ryan Nicola , Brennan Eoin P. , Barry Mary , Perretti Mauro , Belton Orina
Published: January 2021

Background

Atherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis in vivo. In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD).

Methods

miR-155 expression was quantified in aortae from ApoE−/− mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, cis-9,trans-11:trans-10,cis-12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on ex vivo human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD.

Results

Here, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression in vivo. CLA blend also decreased miR-155 expression in vitro in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs.

Conclusion

miR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis in vivo and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.
Mainstreaming Sustainable Consumption of Seafood Through Enhanced Mandatory Food Labeling
Authors: Penca Jerneja
Published: January 2021

To contribute to the debate about sustainable seafood consumption, this article considers the role of mandatory food labeling. The article first flags the rise of a policy paradigm of shared responsibility and policy imperatives at various levels calling for increased integration of the citizen/consumer into public regimes, including in fisheries governance. It then explores the options available to citizen/consumers to engage in the fisheries regime in different stages of the value chain and evaluates their readiness to respond to the expectations. Mandatory food labeling of seafood is introduced as an under-unexplored governance tool, alongside the key enabling technological and policy trends. The rise of transparency and traceability, both as norms and a set of technological capabilities, is highlighted as an opportunity for implementation of mandatory seafood labeling. While recognizing equity challenges and various supplementary actions needed to ensure an effective behavioral and attitudinal shift toward more engaged governance (better education and enforcement and an enabling social setting), the article suggests to further explore mandatory labeling within the governance toolbox. It should be particularly relevant in the context of developed markets with global trade and political influence, and as means of fostering ocean literacy and transparent, participative and deliberative kind of governance.
Nitrification Activity of the Sponge Chondrosia reniformis Under Elevated Concentrations of Ammonium
Authors: Nemoy Philip , Spanier Ehud , Angel Dror L.
Published: January 2021

This study examined the ability of a Mediterranean demosponge Chondrosia reniformis to oxidize exogenous ammonium, simulating N-rich conditions that occur near finfish farms. We hypothesized that as the concentration of ammonium increases in the surrounding seawater, nitrification mediated by microbes associated with C. reniformis will lead to enhancement of ammonium uptake, nitrate excretion and oxygen consumption by the sponge holobiont. To test this hypothesis, we conducted laboratory experiments with C. reniformis explants exposed to ammonium enrichments (300–6667 nM) and to ambient seawater (45–1511 nM ammonium). We analyzed inhaled (IN) and exhaled (EX) water samples for dissolved oxygen, ammonium, nitrates and retention of picoplankton cells. We observed ammonium uptake in nearly half the cases and excretion of nitrate in most experimental outcomes. Yet, the consumption of ammonium and oxygen, as well as the excretion of nitrate by C. reniformis were not related to the concentration of inhaled ammonium, which suggests that the nitrification activity of sponge-associated microbes is not necessarily related to the concentration of ammonium in the surrounding seawater. Further research is required to reveal the sources of nitrate released from sponges and the fate of this nitrate in natural and manipulated ecosystems.
Pre-transplant Sarcopenic Obesity Worsens the Survival After Liver Transplantation: A Meta-Analysis and a Systematic Review
Authors: Hegyi Péter Jenö , Soós Alexandra , Hegyi Péter , Szakács Zsolt , Hanák Lilla , Váncsa Szilárd , Ocskay Klementina , Pétervári Erika , Balaskó Márta , Eröss Bálint , Pár Gabriella
Published: January 2021

Background: The rising prevalence of cirrhotic cases related to non-alcoholic steatohepatitis has led to an increased number of cirrhotic patients with coexistence of obesity and muscle mass loss, known as sarcopenic obesity (SO). In patients undergoing liver transplantation (LT), the presence of SO may worsen prognosis, and increase morbidity and mortality.

Objective: We aimed to evaluate the effect of the presence of pre-transplant SO on the outcomes of LT.

Methods: A comprehensive search was performed in seven medical databases for studies comparing morbidity and mortality of patients with and without SO after LT. The primary outcome was overall mortality in the short- (1 year), intermediate- (3 years), and long- (5 years) term. We calculated pooled relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was quantified with I2-statistics.

Results: Based on the analysis of 1,515 patients from three articles, SO increased overall mortality compared to non-SO at short-, intermediate-, and long-term follow-up (RR = 2.06, 95% CI: 1.28-3.33; RR = 1.67, 95% CI: 1.10-2.51; and RR = 2.08, 95% CI: 1.10-3.93, respectively) without significant between-study heterogeneity for the short- and intermediate- term (I2 = 0.0% for both) and considerable heterogeneity for long-term follow-up (I2 = 81.1%).

Conclusion: Pre-transplant SO proved to be a risk factor after LT and was associated with two times higher mortality at short- and long- term follow-up. Since SO worsens the prognosis of patients after LT, the inclusion of body composition assessment before LT may help to plan a more individualized nutritional treatment, physiotherapy, and postoperative care and may improve morbidity and mortality.
Symbiotic Fungus Affected the Asian Citrus Psyllid (ACP) Resistance to Imidacloprid and Thiamethoxam
Authors: Yi Tuyong , Lei Ling , He Ling , Yi Jianglan , Li Lingguo , Dai Liangying , Hong Yanyun
Published: January 2021

The Asian citrus psyllid (ACP), Diaphorina citri (Kuwayama) (Hemiptera: Liviidae), is a notorious Rutaceae plant pest. Frequent and extensive use of pesticides has resulted in severe insecticide resistance in ACP populations. Fully understanding the mechanism of ACP resistance to pesticides is vital for us to control or delay the development of resistance. Therefore, we compared the difference in resistance to imidacloprid and thiamethoxam between Hunan (Yongzhou, Chenzhou) and Guangdong (Guangzhou) ACP populations and analyzed the correlations between the resistance level and genes and symbiotic fungi. The results showed that the resistance of the Guangdong ACP population to imidacloprid and thiamethoxam was lower than that of Hunan ACP population, and the relative expression of genes associated with P450 mono-oxygenase and acetylcholinesterase was significantly lower in the Guangdong ACP population than in Hunan ACP population. The differences of mean relative abundances of four symbiotic bacteria among three populations were marginally significant; however, the mean relative abundance of 16 fungi among three populations was significantly different, and positive linear correlations were observed between the resistance level and two fungi (Aspergillus niger and Aureobasidium pullulans) and two genes (CYP4C70 and CYP4DB1). Negative correlations were only observed between the resistance level and two fungi (Golubevia pallescens and Acremonium sclerotigenum). Moreover, four fungi were unique to the Chenzhou population which was the highest resistance to imidacloprid and thiamethoxam. These findings suggested the P450 mono-oxygenase and symbiotic fungi together affected ACP resistance to imidacloprid and thiamethoxam. In the future, we may use environmental G. pallescens and A. sclerotigenum to control or delay ACP resistance.
Emergence and Spread of Different ESBL-Producing Salmonella enterica Serovars in Hospitalized Horses Sharing a Highly Transferable IncM2 CTX-M-3-Encoding Plasmid
Authors: Dor Ziv , Shnaiderman-Torban Anat , Kondratyeva Kira , Davidovich-Cohen Maya , Rokney Assaf , Steinman Amir , Navon-Venezia Shiri
Published: January 2021

Salmonella enterica is a major causative pathogen of human and animal gastroenteritis. Antibiotic resistant strains have emerged due to the production of extended-spectrum β-lactamases (ESBLs) posing a major health concern. With the increasing reports on ESBL-producing Enterobacterales that colonize companion animals, we aimed to investigate ESBL dissemination among ESBL-producing Salmonella enterica (ESBL-S) in hospitalized horses. We prospectively collected ESBL-S isolates from hospitalized horses in a Veterinary-Teaching Hospital during Dec 2015–Dec 2017. Selection criteria for ESBL-S were white colonies on CHROMagarESBL plates and an ESBL phenotypic confirmation. Salmonella enterica serovars were determined using the Kaufmann-White-Le-Minor serological scheme. ESBL-encoding plasmids were purified, transformed and compared using restriction fragment length polymorphism (RFLP). Whole genome sequencing (Illumina and MinION platforms) were performed for detailed phylogenetic and plasmid analyses. Twelve ESBL-S were included in this study. Molecular investigation and Sequence Read Archive (SRA) meta-analysis revealed the presence of three unique Salmonella enterica serovars, Cerro, Havana and Liverpool, all reported for the first time in horses. PFGE revealed the clonal spread of S. Cerro between seven horses. All twelve isolates carried blaCTX–M–3 and showed an identical multidrug resistance profile with co-resistance to trimethoprim/sulfamethoxazole and to aminoglycosides. Plasmid RFLP proved the inter-serovar horizontal spread of a single blaCTX–M–3-encoding plasmid. Complete sequence of a representative plasmid (S. Havana strain 373.3.1), designated pSEIL-3 was a -86.4 Kb IncM2 plasmid, that encoded nine antibiotic resistance genes. pSEIL-3 was virtually identical to pCTX-M3 from Citrobacter freundii, and showed high identity (>95%) to six other blaCTX–M–3 or blaNDM–1 IncM2 broad host range plasmids from various Enterobacterales of human origin. Using a specific six gene-based multiplex PCR, we detected pSEIL-3 in various Enterobacterales species that co-colonized the horses’ gut. Together, our findings show the alarming emergence of ESBL-S in hospitalized horses associated with gut shedding and foal morbidity and mortality. We demonstrated the dissemination of CTX-M-3 ESBL among different Salmonella enterica serovars due to transmission of a broad host range plasmid. This report highlights horses as a zoonotic reservoir for ESBL-S, including highly transmissible plasmids that may represent a ‘One-Health’ hazard. This risk calls for the implementation of infection control measures to monitor and control the spread of ESBL-S in hospitalized horses.
Virucidal Action Mechanism of Alcohol and Divalent Cations Against Human Adenovirus
Authors: Martín-González Natalia , Vieira Gonçalves Leonam , Condezo Gabriela N. , San Martín Carmen , Rubiano María , Fallis Ian , Rubino Joseph R. , Ijaz M. Khalid , Maillard Jean-Yves , De Pablo Pedro J.
Published: January 2021

Hygiene and disinfection practices play an important role at preventing spread of viral infections in household, industrial and clinical settings. Although formulations based on >70% ethanol are virucidal, there is a currently a need to reformulate products with much lower alcohol concentrations. It has been reported that zinc can increase the virucidal activity of alcohols, although the reasons for such potentiation is unclear. One approach in developing virucidal formulations is to understand the mechanisms of action of active ingredients and formulation excipients. Here, we investigated the virucidal activity of alcohol (40% w/v) and zinc sulfate (0.1% w/v) combinations and their impact on a human adenovirus (HAdV) using, nucleic acid integrity assays, atomic force microscopy (AFM) and transmission electron microscopy (TEM). We observed no difference in virucidal activity (5 log10 reduction in 60 min) against between an ethanol only based formulation and a formulation combining ethanol and zinc salt. Furthermore, TEM imaging showed that the ethanol only formulation produced gross capsid damage, whilst zinc-based formulation or formulation combining both ethanol and zinc did not affect HAdV DNA. Unexpectedly, the addition of nickel salt (5 mM NiCl2) to the ethanol-zinc formulation contributed to a weakening of the capsid and alteration of the capsid mechanics exemplified by AFM imaging, together with structural capsid damage. The addition of zinc sulfate to the ethanol formulation did not add the formulation efficacy, but the unexpected mechanistic synergy between NiCl2 and the ethanol formulation opens an interesting perspective for the possible potentiation of an alcohol-based formulation. Furthermore, we show that AFM can be an important tool for understanding the mechanistic impact of virucidal formulation.
Development of an Albumin-Based PSMA Probe With Prolonged Half-Life
Authors: Liu Teli , Liu Chen , Ren Yanan , Guo Xiaoyi , Jiang Jinquan , Xie Qing , Xia Lei , Wang Feng , Zhu Hua , Yang Zhi
Published: January 2021

Prostate-specific membrane antigen (PSMA) is an attractive target for the diagnosis and therapy of prostate cancer as it is specifically overexpressed in prostate cancer cells. Improving the circulation of radioligands in the blood is considered as an effective strategy that can improve tumor burden, which benefits detection of small lesions and improves the effect of PSMA radioligand therapy (PRLT). In this study, we introduced maleimidopropionic acid (MPA) to a PSMA-targeted tracer and developed Al18F-PSMA-CM, which targets human serum albumin (HSA) binding and PSMA. Al18F-PSMA-CM is evaluated in vitro and in vivo for stability, PSMA specificity, and biodistribution in 22Rv1 tumor-bearing mice. Al18F-PSMA-CM was prepared with a radiochemical purity of >99% and specific activity of 11.22–18.70 MBq/nmol. Al18F-PSMA-CM was stable in vitro and in vivo and prolonged circulation in blood with a binding ratio of 47 ± 3.2% and Kd value of 3.08 ± 0.45 nM to HSA. The uptake of Al18F-PSMA-CM in PSMA(+) 22Rv1 cells was increased in 2 h, and the uptake was blocked by a PSMA inhibitor, ZJ-43. The Kd value of Al18F-PSMA-CM to PSMA was 8.46 ± 0.24 nM. Al18F-PSMA-CM was accumulated in kidneys and 22Rv1 tumors [74.76 ± 15.42 and 6.16 ± 0.74 ID%/g at 2 h post injection (p.i.)], which were decreased by −80.0 and −84.3% when co-injected with ZJ-43. Al18F-PSMA-CM showed high PSMA specificity and accumulated in 22Rv1 tumors with increasing uptake in 4 h. MPA moiety showed the ability to prolong the half-life of tracers, and the MPA-conjugated tracer showed the potential to improve tumor uptake. MPA may be a choice to develop radiopharmaceuticals for PRLT of prostate cancer.
Association Between Hearing Characteristics/Prognosis and Vestibular Function in Sudden Sensorineural Hearing Loss With Vertigo
Authors: Wang Yixu , Wang Le , Jing Yuanyuan , Yu Lisheng , Ye Fanglei
Published: January 2021

Sudden sensorineural hearing loss (SSNHL) patients with vertigo have a poorer prognosis. However, the factors associated with hearing recovery remain uncertain. This retrospective study was to evaluate the association between hearing characteristics/hearing recovery and the patterns of vestibulocochlear lesions in SSNHL patients with vertigo. Patients were classified into groups according to the patterns of vestibular dysfunction. We not only compared hearing characteristics and prognosis among subgroups but also determined the potential association between vestibular lesion location and hearing recovery. The shapes of the audiogram differed significantly between patients with normal vestibular function and patients with vestibular dysfunction (p = 0.022). Patients whose audiogram indicated profound hearing loss were 3.89 times more likely to have vestibular dysfunction than those whose audiogram shape indicated low-frequency hearing loss (95% CI, 1.02–14.86, p = 0.047). Patients who had saccule dysfunction were 0.11 times as likely to have hearing recovery than those who had normal saccule function (95% CI, 0.11–0.31, p = 0.001). When adjusted for sex and age, patients who had saccule dysfunction were 0.07 times as likely to have hearing recovery than those who had normal saccule function (95% CI, 0.02–0.22, p = 0.001). Abnormal results following cVEMP testing may be a potential predictive factor for poor hearing recovery.