bluuebunny/crossref_metadata_2025 huggingface dataset:
HANDHELD THERMAL VISION DEVICES WITH VARIABLE CHARACTERISTICS
Authors:   Siberian State University of Geosystems and Technologies, Khatsevich Tatyana N. , Druzhkin Evgeniy V. ,   LUGGAR Co Ltd, Volkova Ksenia D. ,   Optical Design Office Co Ltd
Published: December 2020

The intensive development of thermal imaging device is accompanied by the expansion of its functional possibilities. One of them is the realization of changing magnifications and fields. The aim of the work is to justify the method of changing focal lengths and fields, ensuring the constancy of the relative aperture and axial length of the lenses when changing the field in thermal imaging devices using uncooled microbolometer infrared sensor arrays. A method of structural synthesis of a lens of three components is proposed. The method is characterized by the following: the optical power of the first component is equal to the optical power of the lens, the sum of the optical powers of the second and third components is zero. The aperture diaphragm is located on the third component. The internal component has two discrete positions. Relations between the parameters of components that are found provide the invariability of the back focal length and the relative aperture of the lens when changing the focal length. The capabilities of the method are confirmed by the development of four infrared lenses with two- and three-fold differences in focal lengths. Decreasing the length along the axis and the stability of the relative aperture of the lens with diffractive image qual-ity when changing the focal length in an optical scheme with a bi-aspheric design is achieved.
CREATING METRIC SIMULATED MODEL OF A "DIGITAL TWIN" BY THE ACTIVE EARTH REMOTE SENSING METHOD
Authors:   Siberian State University of Geosystems and Technologies, Altyntsev Maxim A. , Karpik Pavel A. ,   Novosibirsk State University
Published: December 2020

Recently, a line of research devoted to the creation of three-dimensional metric simulated models of digital twins has been actively developing. The goal of creating digital twins is to transfer the complicated manufacturing processes, that are performed while monitoring the state of real objects, to a computer environment where a three-dimensional information model was first created. The key requirements are accuracy and efficiency within the conditions of design, construction and operation of real objects when making changes to them. These requirements are met by an active method of the Earth remote sensing, such as laser scanning. Terrestrial laser scanning is used to model objects over a relatively small area and to achieve maximum accuracy. The task of creating digital twin models poses higher requirements for choosing a field stage laser scanning technique and has many features when performing three-dimensional modeling using field data. The article proposes technique of three-dimensional modeling for creating building information models. It analyses the accuracy of the terrestrial laser scanning results. A warehouse space to be reconstructed was selected as the subject of the study. Using the example of laser scanning data for this object, it was indicated that the method under consideration allows ensuring the accuracy of creating a three-dimensional information model up to 1 cm. The laser scanning data of the object show that the considered method ensures 3D information model accuracy up to 1 cm.
Disentangling Biomolecular Corona Interactions With Cell Receptors and Implications for Targeting of Nanomedicines
Authors: Aliyandi Aldy , Zuhorn Inge S. , Salvati Anna
Published: December 2020

Nanoparticles are promising tools for nanomedicine in a wide array of therapeutic and diagnostic applications. Yet, despite the advances in the biomedical applications of nanomaterials, relatively few nanomedicines made it to the clinics. The formation of the biomolecular corona on the surface of nanoparticles has been known as one of the challenges toward successful targeting of nanomedicines. This adsorbed protein layer can mask targeting moieties and creates a new biological identity that critically affects the subsequent biological interactions of nanomedicines with cells. Extensive studies have been directed toward understanding the characteristics of this layer of biomolecules and its implications for nanomedicine outcomes at cell and organism levels, yet several aspects are still poorly understood. One aspect that still requires further insights is how the biomolecular corona interacts with and is “read” by the cellular machinery. Within this context, this review is focused on the current understanding of the interactions of the biomolecular corona with cell receptors. First, we address the importance and the role of receptors in the uptake of nanoparticles. Second, we discuss the recent advances and techniques in characterizing and identifying biomolecular corona-receptor interactions. Additionally, we present how we can exploit the knowledge of corona-cell receptor interactions to discover novel receptors for targeting of nanocarriers. Finally, we conclude this review with an outlook on possible future perspectives in the field. A better understanding of the first interactions of nanomaterials with cells, and -in particular -the receptors interacting with the biomolecular corona and involved in nanoparticle uptake, will help for the successful design of nanomedicines for targeted delivery.
Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models
Authors: Thompson Clare L. , Fu Su , Heywood Hannah K. , Knight Martin M. , Thorpe Stephen D.
Published: December 2020

Organ-on-chip (OOC) systems recapitulate key biological processes and responses in vitro exhibited by cells, tissues, and organs in vivo. Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of in vivo behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating in vivo physiology in health and disease.
Bcl11b/Ctip2 in Skin, Tooth, and Craniofacial System
Authors: Daher Marie-Thérèse , Bausero Pedro , Agbulut Onnik , Li Zhenlin , Parlakian Ara
Published: December 2020

Ctip2/Bcl11b is a zinc finger transcription factor with dual action (repression/activation) that couples epigenetic regulation to gene transcription during the development of various tissues. It is involved in a variety of physiological responses under healthy and pathological conditions. Its role and mechanisms of action are best characterized in the immune and nervous systems. Furthermore, its implication in the development and homeostasis of other various tissues has also been reported. In the present review, we describe its role in skin development, adipogenesis, tooth formation and cranial suture ossification. Experimental data from several studies demonstrate the involvement of Bcl11b in the control of the balance between cell proliferation and differentiation during organ formation and repair, and more specifically in the context of stem cell self-renewal and fate determination. The impact of mutations in the coding sequences of Bcl11b on the development of diseases such as craniosynostosis is also presented. Finally, we discuss genome-wide association studies that suggest a potential influence of single nucleotide polymorphisms found in the 3’ regulatory region of Bcl11b on the homeostasis of the cardiovascular system.
α-Actinin-4 Promotes the Progression of Prostate Cancer Through the Akt/GSK-3β/β-Catenin Signaling Pathway
Authors: Park Sungyeon , Kang Minsoo , Kim Suhyun , An Hyoung-Tae , Gettemans Jan , Ko Jesang
Published: December 2020

The first-line treatment for prostate cancer (PCa) is androgen ablation therapy. However, prostate tumors generally recur and progress to androgen-independent PCa (AIPC) within 2–3 years. α-Actinin-4 (ACTN4) is an actin-binding protein that belongs to the spectrin gene superfamily and acts as an oncogene in various cancer types. Although ACTN4 is involved in tumorigenesis and the epithelial–mesenchymal transition of cervical cancer, the role of ACTN4 in PCa remains unknown. We found that the ACTN4 expression level increased during the transition from androgen-dependent PCa to AIPC. ACTN4 overexpression resulted in enhanced proliferation and motility of PCa cells. Increased β-catenin due to ACTN4 promoted the transcription of genes involved in proliferation and metastasis such as CCND1 and ZEB1. ACTN4-overexpressing androgen-sensitive PCa cells were able to grow in charcoal-stripped media. In contrast, ACTN4 knockdown using si-ACTN4 and ACTN4 nanobody suppressed the proliferation, migration, and invasion of AIPC cells. Results of the xenograft experiment revealed that the mice injected with LNCaPACTN4 cells exhibited an increase in tumor mass compared with those injected with LNCaPMock cells. These results indicate that ACTN4 is involved in AIPC transition and promotes the progression of PCa.
Dihydroartemisinin Sensitizes Esophageal Squamous Cell Carcinoma to Cisplatin by Inhibiting Sonic Hedgehog Signaling
Authors: Cui Wei , Fang Tingting , Duan Zhaoheng , Xiang Dongfang , Wang Yanxia , Zhang Mengsi , Zhai Fangzheng , Cui Xiang , Yang Lang
Published: December 2020

Platinum-based regimens have been routinely used in the clinical treatment of patients with esophageal squamous cell carcinoma (ESCC). However, administration of these drugs is frequently accompanied by drug resistance. Revealing the underlying mechanisms of the drug resistance and developing agents that enhance the sensitivity to platinum may provide new therapeutic strategies for the patients. In the present study, we found that the poor outcome of ESCC patients receiving platinum-based regimens was associated with co-expression of Shh and Sox2. The sensitivity of ESCC cell lines to cisplatin was related to their activity of Shh signaling. Manipulating of Shh expression markedly changed the sensitivity of ESCC cells to platinum. Continuous treatment with cisplatin resulted in the activation of Shh signaling and enhanced cancer stem cell-like phenotypes in ESCC cells. Dihydroartemisinin (DHA), a classic antimalarial drug, was identified as a novel inhibitor of Shh pathway. Treatment with DHA attenuated the cisplatin-induced activation of the Shh pathway in ESCC cells and synergized the inhibitory effect of cisplatin on proliferation, sphere and colony formation of ALDH-positive ESCC cells in vitro and growth of ESCC cell-derived xenograft tumors in vivo. Taken together, these results demonstrate that the Shh pathway is an important player in cisplatin-resistant ESCC and DHA acts as a promising therapeutic agent to sensitize ESCC to cisplatin treatment.
b3galt6 Knock-Out Zebrafish Recapitulate β3GalT6-Deficiency Disorders in Human and Reveal a Trisaccharide Proteoglycan Linkage Region
Authors: Delbaere Sarah , De Clercq Adelbert , Mizumoto Shuji , Noborn Fredrik , Bek Jan Willem , Alluyn Lien , Gistelinck Charlotte , Syx Delfien , Salmon Phil L. , Coucke Paul J. , Larson Göran , Yamada Shuhei , Willaert Andy , Malfait Fransiska
Published: December 2020

Proteoglycans are structurally and functionally diverse biomacromolecules found abundantly on cell membranes and in the extracellular matrix. They consist of a core protein linked to glycosaminoglycan chains via a tetrasaccharide linkage region. Here, we show that CRISPR/Cas9-mediatedb3galt6knock-out zebrafish, lacking galactosyltransferase II, which adds the third sugar in the linkage region, largely recapitulate the phenotypic abnormalities seen in human β3GalT6-deficiency disorders. These comprise craniofacial dysmorphism, generalized skeletal dysplasia, skin involvement and indications for muscle hypotonia. In-depth TEM analysis revealed disturbed collagen fibril organization as the most consistent ultrastructural characteristic throughout different affected tissues. Strikingly, despite a strong reduction in glycosaminoglycan content, as demonstrated by anion-exchange HPLC, subsequent LC-MS/MS analysis revealed a small amount of proteoglycans containing a unique linkage region consisting of only three sugars. This implies that formation of glycosaminoglycans with an immature linkage region is possible in a pathogenic context. Our study, therefore unveils a novel rescue mechanism for proteoglycan production in the absence of galactosyltransferase II, hereby opening new avenues for therapeutic intervention.
The Recycling Endosome in Nerve Cell Development: One Rab to Rule Them All?
Authors: Rozés-Salvador Victoria , González-Billault Christian , Conde Cecilia
Published: December 2020

Endocytic recycling is an intracellular process that returns internalized molecules back to the plasma membrane and plays crucial roles not only in the reuse of receptor molecules but also in the remodeling of the different components of this membrane. This process is required for a diversity of cellular events, including neuronal morphology acquisition and functional regulation, among others. The recycling endosome (RE) is a key vesicular component involved in endocytic recycling. Recycling back to the cell surface may occur with the participation of several different Rab proteins, which are master regulators of membrane/protein trafficking in nerve cells. The RE consists of a network of interconnected and functionally distinct tubular subdomains that originate from sorting endosomes and transport their cargoes along microtubule tracks, by fast or slow recycling pathways. Different populations of REs, particularly those formed by Rab11, Rab35, and Arf6, are associated with a myriad of signaling proteins. In this review, we discuss the cumulative evidence suggesting the existence of heterogeneous domains of REs, controlling different aspects of neurogenesis, with a particular focus on the commonalities and singularities of these REs and their contribution to nerve development and differentiation in several animal models.
Severe Acute Respiratory Syndrome Coronavirus 2-Induced Neurological Complications
Authors: Yu Shijia , Yu Mingjun
Published: December 2020

Our review aims to highlight the neurological complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the available treatments according to the existing literature, discussing the underlying mechanisms. Since the end of 2019, SARS-CoV-2 has induced a worldwide pandemic that has threatened numerous lives. Fever, dry cough, and respiratory symptoms are typical manifestations of COVID-19. Recently, several neurological complications of the central and peripheral nervous systems following SARS-CoV-2 infection have gained clinicians' attention. Encephalopathy, stroke, encephalitis/meningitis, Guillain–Barré syndrome, and multiple sclerosis are considered probable neurological signs of COVID-19. The virus may invade the nervous system directly or induce a massive immune inflammatory response via a “cytokine storm.” Specific antiviral drugs are still under study. To date, immunomodulatory therapies and supportive treatment are the predominant strategies. In order to improve the management of COVID-19 patients, it is crucial to monitor the onset of new neurological complications and to explore drugs/vaccines targeted against SARS-CoV-2 infection.
Quercetin Suppresses Apoptosis and Attenuates Intervertebral Disc Degeneration via the SIRT1-Autophagy Pathway
Authors: Wang Dong , He Xin , Wang Di , Peng Pandi , Xu Xiaolong , Gao Bo , Zheng Chao , Wang Han , Jia Haoruo , Shang Qiliang , Sun Zhen , Luo Zhuojing , Yang Liu
Published: December 2020

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which causes an enormous socioeconomic burden. Previous studies demonstrated that the apoptosis of nucleus pulposus (NP) cells and the dyshomeostasis of extracellular matrix (ECM) contributed to the pathogenesis of IDD, and effective therapies were still lacking. Quercetin, a natural flavonoid possessing a specific effect of autophagy stimulation and SIRT1 activation, showed some protective effect on a series of degenerative diseases. Based on previous studies, we hypothesized that quercetin might have therapeutic effects on IDD by inhibiting the apoptosis of NP cells and dyshomeostasis of ECM via the SIRT1-autophagy pathway. In this study, we revealed that quercetin treatment inhibited the apoptosis of NP cells and ECM degeneration induced by oxidative stress. We also found that quercetin promoted the expression of SIRT1 and autophagy in NP cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) reversed the protective effect of quercetin on apoptosis and ECM degeneration. Moreover, SIRT1 enzymatic activity inhibitor EX-527, suppressed quercetin-induced autophagy and the protective effect on NP cells, indicating that quercetin protected NP cells against apoptosis and prevented ECM degeneration via SIRT1-autophagy pathway. In vivo, quercetin was also demonstrated to alleviate the progression of IDD in rats. Taken together, our results suggest that quercetin prevents IDD by promoting SIRT1-dependent autophagy, indicating one novel and effective therapeutic method for IDD.
On the Efficient Evaluation of the Exchange Correlation Potential on Graphics Processing Unit Clusters
Authors: Williams-Young David B. , de Jong Wibe A. , van Dam Hubertus J. J. , Yang Chao
Published: December 2020

The predominance of Kohn–Sham density functional theory (KS-DFT) for the theoretical treatment of large experimentally relevant systems in molecular chemistry and materials science relies primarily on the existence of efficient software implementations which are capable of leveraging the latest advances in modern high-performance computing (HPC). With recent trends in HPC leading toward increasing reliance on heterogeneous accelerator-based architectures such as graphics processing units (GPU), existing code bases must embrace these architectural advances to maintain the high levels of performance that have come to be expected for these methods. In this work, we purpose a three-level parallelism scheme for the distributed numerical integration of the exchange-correlation (XC) potential in the Gaussian basis set discretization of the Kohn–Sham equations on large computing clusters consisting of multiple GPUs per compute node. In addition, we purpose and demonstrate the efficacy of the use of batched kernels, including batched level-3 BLAS operations, in achieving high levels of performance on the GPU. We demonstrate the performance and scalability of the implementation of the purposed method in the NWChemEx software package by comparing to the existing scalable CPU XC integration in NWChem.
Design and Optimization of Quinazoline Derivatives: New Non-nucleoside Inhibitors of Bovine Viral Diarrhea Virus
Authors: Fernández Gabriela A. , Castro Eliana F. , Rosas Rocío A. , Fidalgo Daniela M. , Adler Natalia S. , Battini Leandro , España de Marco Maria J. , Fabiani Matias , Bruno Ana M. , Bollini Mariela , Cavallaro Lucia V.
Published: December 2020

Bovine viral diarrhea virus (BVDV) belongs to the Pestivirus genus (Flaviviridae). In spite of the availability of vaccines, the virus is still causing substantial financial losses to the livestock industry. In this context, the use of antiviral agents could be an alternative strategy to control and reduce viral infections. The viral RNA-dependent RNA polymerase (RdRp) is essential for the replication of the viral genome and constitutes an attractive target for the identification of antiviral compounds. In a previous work, we have identified potential molecules that dock into an allosteric binding pocket of BVDV RdRp via a structure-based virtual screening approach. One of them, N-(2-morpholinoethyl)-2-phenylquinazolin-4-amine [1, 50% effective concentration (EC50) = 9.7 ± 0.5 μM], was selected to perform different chemical modifications. Among 24 derivatives synthesized, eight of them showed considerable antiviral activity. Molecular modeling of the most active compounds showed that they bind to a pocket located in the fingers and thumb domains in BVDV RdRp, which is different from that identified for other non-nucleoside inhibitors (NNIs) such as thiosemicarbazone (TSC). We selected compound 2-[4-(2-phenylquinazolin-4-yl)piperazin-1-yl]ethanol (1.9; EC50 = 1.7 ± 0.4 μM) for further analysis. Compound 1.9 was found to inhibit the in vitro replication of TSC-resistant BVDV variants, which carry the N264D mutation in the RdRp. In addition, 1.9 presented adequate solubility in different media and a high-stability profile in murine and bovine plasma.
Electrocatalytic Oxidation of Methanol by a Polymeric Ni Complex-Modified Electrode Prepared by a One-Step Cold-Plasma Process
Authors: Jeon Ji-Soo , Yu In-Keun , Kim Woonjung , Choi Seong-Ho
Published: December 2020

In this work, a polymeric nickel complex-modified indium tin oxide (ITO) electrode was prepared by a one-step cold-plasma process of acrylic-Ni complex precursors. Also, the work provides the electrocatalytic oxidation of methanol by a polymeric Ni complex-modified electrode prepared by a simple one-step cold-plasma process. The acrylic-Ni complex precursors were synthesized by complexation of nickel (II) chloride, and acrylic acid in a small amount of water; subsequently we added N,N′-methylene-bis-acrylamide as a crosslinking agent to the complex solution. We characterized the prepared polymeric Ni complex-modified (Ni-modified) catalytic electrode by X-ray photoelectron spectroscopy, field emission scanning electron microscopy, and electrochemical methods. Electrochemical characterization showed stable redox behavior of Ni(III)/Ni(II) couples. Cyclic voltammetric experiments have shown that electrocatalytic oxidation of methanol can occur on Ni-modified catalytic electrodes, while not observed on bare ITO. As a result, this work provides the simple and easy preparation of electrocatalysts by one-step plasma process for methanol fuel cell.
First-Principle Insight Into the Effects of Oxygen Vacancies on the Electronic, Photocatalytic, and Optical Properties of Monoclinic BiVO4(001)
Authors: Gu Xiaosong , Luo Yujie , Li Qi , Wang Rui , Fu Shiqi , Lv Xiulong , He Qian , Zhang Ying , Yan Qiutong , Xu Xuan , Ji Fangying , Qiu Yan
Published: December 2020

In this paper, first-principle calculations were performed to investigate the effects of oxygen (O) vacancies (Ovac) on the crystal structure, electronic distribution, adsorption energies of O2 and H2O and the density of states (DOS) of monoclinic bismuth vanadate (m-BiVO4). Ovac were stable when incorporated into m-BiVO4(001) and increased the adsorption energy of O2. Ovac changed the V3d orbitals of m-BiVO4(001) by adding a new band gap level, causing the redundant electrons of V atoms to become carriers and promoting the separation efficiency of electrons and holes. To verify the first-principle calculations, m-BiVO4 with different Ovac levels was prepared via hydrothermal synthesis. X-ray diffraction (XRD) patterns confirmed the existence of the (001) crystal surface of m-BiVO4. In addition, X-ray photoelectron spectroscopy (XPS) and electron spin resonance (ESR) spectroscopy of m-BiVO4 confirmed the presence of Ovac and demonstrated that, as the Ovac level increased, the number of superoxide radicals (O2-·) and hydroxyl radicals (·OH) produced increased. In addition, m-BiVO4 with a higher Ovac level possessed superior photocatalytic properties to and degraded rhodamine B (RhB) dye nearly 2-fold faster than m-BiVO4 with a lower Ovac level. Finally, the removal rate of RhB increased from 23 to 44%. All experimental results were in good agreement with the first-principle calculated results.
Biocatalytic Synthesis of D-Allulose Using Novel D-Tagatose 3-Epimerase From Christensenella minuta
Authors: Wang Yang , Ravikumar Yuvaraj , Zhang Guoyan , Yun Junhua , Zhang Yufei , Parvez Amreesh , Qi Xianghui , Sun Wenjing
Published: December 2020

D-allulose, which is one of the important rare sugars, has gained significant attention in the food and pharmaceutical industries as a potential alternative to sucrose and fructose. Enzymes belonging to the D-tagatose 3-epimerase (DTEase) family can reversibly catalyze the epimerization of D-fructose at the C3 position and convert it into D-allulose by a good number of naturally occurring microorganisms. However, microbial synthesis of D-allulose is still at its immature stage in the industrial arena, mostly due to the preference of slightly acidic conditions for Izumoring reactions. Discovery of novel DTEase that works at acidic conditions is highly preferred for industrial applications. In this study, a novel DTEase, DTE-CM, capable of catalyzing D-fructose into D-allulose was applications. In this study, a novel DTEase, DTE-CM, capable of catalyzing D-fructose into D-allulose was DTE-CM on D-fructose was found to be remarkably influenced and modulated by the type of metal ions (co-factors). The DTE-CM on D-fructose was found to be remarkably influenced and modulated by the type of metal ions (co-factors). The 50°C from 0.5 to 3.5 h at a concentration of 0.1 mM. The enzyme exhibited its maximum catalytic activity on D-fructose at pH 6.0 and 50°C from 0.5 to 3.5 h at a concentration of 0.1 mM. The enzyme exhibited its maximum catalytic activity on -fructose at pH 6.0 and 50°C with a Kcat/Km value of 45 mM−1min−1. The 500 g/L D-fructose, which corresponded to 30% conversion rate. With these interesting catalytic properties, this enzyme could be a promising candidate for industrial biocatalytic applications.
Characterization of Three Porcine Acinetobacter towneri Strains Co-Harboring tet(X3) and blaOXA-58
Authors: Ma Jiangang , Wang Juan , Feng Jie , Liu Yingqiu , Yang Baowei , Li Ruichao , Bai Li , He Tao , Wang Xinglong , Yang Zengqi
Published: December 2020

Tigecycline is the antibiotic of last resort for the treatment of extensively drug-resistant bacterial infections, mainly those of multidrug-resistant Gram-negative bacteria. The plasmid-mediated tet(X3) gene has recently been described in various pathogens that are resistant to tigecycline. We report three tigecycline-resistant Acinetobacter towneri strains isolated from porcine faeces in China, which all contained the tet(X3)-harboring plasmids. A broth microdilution method was used to examine the antimicrobial susceptibility of the isolates, and S1-Nuclease digestion pulsed-field gel electrophoresis (S1-PFGE) was used to characterize their plasmid profiles. The whole-genome sequences of the isolates were determined with the Nanopore PromethION platform. The sequence analysis indicated that the strains were A. towneri. They showed resistance to multiple antibiotics, and all the resistance genes were located on plasmids. The three tet(X3)-harboring plasmids had a similar backbone structure, and all contained blaOXA-58 with various insertion elements (IS). ISCR2 is considered an important factor in tet(X3) mobilization. In addition to ISCR2, we demonstrate that IS26 generates a circular intermediate containing the tet(X3) gene, which could increase the dissemination risk. To our knowledge, this is the first report of tet(X3)- and blaOXA-58-harboring plasmids in A. towneri. Because the IS26 is frequently found in front of tet(X3), research should be directed toward the action of IS26 in the spread of tet(X3).
Guanylate-Binding Proteins Are Critical for Effective Control of Francisella tularensis Strains in a Mouse Co-Culture System of Adaptive Immunity
Authors: Mohammadi Nasibeh , Lindgren Helena , Golovliov Igor , Eneslätt Kjell , Yamamoto Masahiro , Martin Amandine , Henry Thomas , Sjöstedt Anders
Published: December 2020

Francisella tularensisis a Select Agent that causes the severe disease tularemia in humans and many animal species. The bacterium demonstrates rapid intracellular replication, however, macrophages can control its replication if primed and activation with IFN-γ is known to be essential, although alone not sufficient, to mediate such control. To further investigate the mechanisms that control intracellularF. tularensisreplication, anin vitroco-culture system was utilized containing splenocytes obtained from naïve or immunized C57BL/6 mice as effectors and infected bone marrow-derived wild-type or chromosome-3-deficient guanylate-binding protein (GBP)-deficient macrophages. Cells were infected either with theF. tularensislive vaccine strain (LVS), the highly virulent SCHU S4 strain, or the surrogate forF. tularensis,F. novicida. Regardless of strain, significant control of the bacterial replication was observed in co-cultures with wild-type macrophages and immune splenocytes, but not in cultures with immune splenocytes andGBPchr3-deficient macrophages. Supernatants demonstrated very distinct, infectious agent-dependent patterns of 23 cytokines, whereas the cytokine patterns were only marginally affected by the presence or absence of GBPs. Levels of a majority of cytokines were inversely correlated to the degree of control of the SCHU S4 and LVS infections, but this was not the case for theF. novicidainfection. Collectively, the co-culture assay based on immune mouse-derived splenocytes identified a dominant role of GBPs for the control of intracellular replication of variousF. tularensisstrains, regardless of their virulence, whereas the cytokine patterns markedly were dependent on the infectious agents, but less so on GBPs.
Monitoring Spatial and Temporal Differences in Andean Snow Depth Derived From Satellite Tri-Stereo Photogrammetry
Authors: Shaw Thomas E. , Deschamps-Berger César , Gascoin Simon , McPhee James
Published: December 2020

Quantifying the high elevation winter snowpack in mountain environments is crucial for lowland water supply, though it is notoriously difficult to accurately estimate due to a lack of observations and/or uncertainty in the distribution of meteorological variables in space and time. We compare high spatial resolution (3 m), satellite-derived snow depth maps for two drought years (2017 and 2019) in a high mountain catchment of the central Chilean Andes, applying a recently updated methodology for spaceborne photogrammetry. Regional weather station observations revealed an 80% reduction in precipitation for 2019 (the second driest winter since 1950) relative to 2017, though only a 10% reduction in total snow-covered area is seen in the satellite imagery. We threshold surface height changes based upon uncertainty of stable (snow-free) terrain differences for topographic characteristics of the catchment (slope, aspect, roughness etc). For a conservative analysis of change, outside of the topographically-derived confidence intervals, we calculate a mean 0.48 ± 0.28 m reduction of snow depth and a 39 ± 15% reduction in snow volume for 2019, relative to 2017 (for 23% of the total catchment area). Our findings therefore quantify, for the first time in the Andes, the relationship of high-resolution mountain snow depth observations with low elevation precipitation records and characterise its inter-annual variability over high elevation, complex terrain. The practical use of such detailed snow depth information at high elevations is of great value to lowland communities and our findings highlight the clear need to relate the high spatial (Pléiades) and temporal (in-situ) scales within the available datasets in order to improve estimates of region-wide snow volumes.
Newly Discovered Triassic Lithium Deposits in the Dahongliutan Area, NorthWest China: A Case Study for the Detection of Lithium-Bearing Pegmatite Deposits in Rugged Terrains Using Remote-Sensing Data and Images
Authors: Gao Yongbao , Bagas Leon , Li Kan , Jin Moushun , Liu Yuegao , Teng Jiaxin
Published: December 2020

Rare metals, such as lithium and cobalt used in rechargeable batteries, have increased in value as demands for them escalates. Concentrations of lithium-bearing minerals are found in closed-basin brines, granitic pegmatites, and associated granitic rocks containing spodumene (LiAl(SiO3)2) and various other economic minerals. The recently discovered Dahongliutan Li mineral occurrences are hosted by a pegmatite dyke swarm in NW China, in an area that is also prospective for Be, Rb, Nb, and Ta mineralisation. However, the high altitude and steep topography in the area make it extremely difficult to explore for mineralisation. A combination of geochemical methods, geological mapping, and high-resolution remotely sensed multispectral imagery has been used in this study to pinpoint potential locations of pegmatite-hosted Li occurrences. The exploration method developed has led to the discovery many large Li mineral occurrences in the Bayankala Fold Belt, including the 505, 507, north 509, and South Fulugou 1# and 2# mineral occurrences (documented here) with a combined resource of over 1.7 million tonnes (Mt). The laser ablation multi-receiver inductively coupled plasma mass spectrometer (LA-MC-ICP-MS)206Pb/207Pb-238U/207Pb isochron age of the mineralised pegmatite is 223 ± 11 Ma (N = 44, MSWD = 2.1). The40Ar/39Ar plateau age of muscovite in the mineralised pegmatite dates between 197 ± 1 and 185 ± 1 Ma. These dates show that these granitic pegmatites (with a monzogranitic composition) were emplaced during the Late Triassic coeval with magmatism in the region. Our data show that the Li mineralisation in the Dahongliutan area has a similar age and genesis as the pegmatite-hosted deposits of the Jiajika area in the western Sichuan Province. This indicates that the Dahongliutan area is highly prospective of various pegmatite-hosted mineral deposits.
Do Service Learning and Active-Citizenship Learning Support Our Students to Live a Culture of Democracy?
Authors: Geier Ingrid , Hasager Ulla
Published: December 2020

Civic thinking and civic attitude require values and norms for social togetherness and social engagement. Service learning and active-citizenship learning are high-impact pedagogies, well-documented as supporting civic-mindedness and a culture of democracy sustainably. Though our study is part of a broader research project, this brief research report already documents the impact of the two pedagogies on civic-mindedness and students' democratic awareness. Through a mixed-method design we implemented a quantitative survey (7 level Likert Scale) of undergraduate student learning outcomes of service learning with 55 students from the University of Hawai'i at Mānoa and 41 students practicing active-citizenship learning at Salzburg University of Teacher Education. We found that the two pedagogies significantly support students' democratic awareness and civic attitudes. In addition to the survey, a qualitative analysis is in progress based on 23 focus group discussions, conducted to detail how the students experience themselves when they take on social responsibility, e.g., when they actively participate in improving their society. Our mixed, but narrowly focused, approach combined with well-established measuring tools and scales is a first study of how to assess Attitudes, one of the four fundamental principles of the Council of Europe‘s Competency Model for a Democratic Culture.
Further Development of Small Hydropower Facilities May Alter Nutrient Transport to the Pantanal Wetland of Brazil
Authors: Oliveira Marcia Divina de , Fantin-Cruz Ibraim , Campos Juliana Andrade , Campos Marcel Medina de , Mingoti Rafael , Souza Marcelo Luiz de , Figueiredo Daniela Maimoni de , Dores Eliana Freire Gaspar de Carvalho , Pedrollo Olavo , Hamilton Stephen K.
Published: December 2020

Small hydropower (SHP) facilities, defined variably but usually by installed capacities of <10–50 MW, are proliferating around the world, particularly in tropical and subtropical regions. Compared to larger dams, SHPs are generally viewed as having less environmental impact, although there has been little research to support that assertion. Numerous SHPs have been built, and many more are in development or proposed, in rivers that drain into the Pantanal, a world-renowned floodplain wetland system located mostly in Brazil. The upland tributaries are important sources of nutrients to the Pantanal, affecting the biological productivity of downstream floodplains. This study presents measurements from upstream and downstream of 25 current hydropower facilities, most of which are SHPs, throughout the upland watersheds of the Upper Paraguay River basin to reveal how these facilities may affect the concentrations and transport of nutrients in rivers flowing to the Pantanal. Artificial neural network models estimated the impact of building 80 future SHPs on nutrient transport into the Pantanal, based on observations at current facilities as well as the spatial distribution of future facilities. Overall impacts of current hydropower facilities were not large, and in most cases were indistinguishable based on comparisons between upstream and downstream. The short water residence times of reservoirs associated with SHPs likely explain their tendency to have little or no effect on nutrient transport. However, model predictions for hydropower facilities that may be built in the future, many on rivers with higher discharge and sediment loads, point to significant reductions in overall TN (8%) and TP (29%) transport, with potential negative consequences for river and floodplain productivity. Negative impacts may be either because the rivers carry low nutrient concentrations and are thereby sensitive to oligotrophication, or they are particularly important overall nutrient sources supporting ecosystem productivity in downstream rivers and floodplains. Together with a parallel study of sediment transport, these results support recommendations that several river systems presently lacking dams in their lower reaches should be excluded from future hydropower development to maintain the nutrient and sediment supply to the Pantanal.
Integrative Analysis Reveals Common and Unique Roles of Tetraspanins in Fibrosis and Emphysema
Authors: Tripathi Lokesh P. , Itoh Mari N. , Takeda Yoshito , Tsujino Kazuyuki , Kondo Yasushi , Kumanogoh Atsushi , Mizuguchi Kenji
Published: December 2020

While both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are multifactorial disorders characterized by distinct clinical and pathological features, their commonalities and differences have not been fully elucidated. We sought to investigate the preventive roles of tetraspanins Cd151 and Cd9 -that are involved in diverse cellular processes in lung pathophysiology- in pulmonary fibrosis and emphysema, respectively, and to obtain a deeper understanding of their underlying molecular mechanisms toward facilitating improved therapeutic outcomes. Using an integrative approach, we examined the transcriptomic changes in the lungs of Cd151- and Cd9-deficient mice using functional-enrichment-analysis, pathway-perturbation-analysis and protein-protein-interaction (PPI) network analysis. Circadian-rhythm, extracellular-matrix (ECM), cell-adhesion and inflammatory responses and associated factors were prominently influenced by Cd151-deletion. Conversely, cellular-junctions, focal-adhesion, vascular-remodeling, and TNF-signaling were deeply impacted by Cd9-deletion. We also highlighted a “common core” of factors and signaling cascades that underlie the functions of both Cd151 and Cd9 in lung pathology. Circadian dysregulation following Cd151-deletion seemingly facilitated progressive fibrotic lung phenotype. Conversely, TGF-β signaling attenuation and TNF-signaling activation emerged as potentially novel functionaries of Cd9-deletion-induced emphysema. Our findings offer promising avenues for developing novel therapeutic treatments for pulmonary fibrosis and emphysema.
Dynamic SARS-CoV-2-Specific Immunity in Critically Ill Patients With Hypertension
Authors: Zeng Qiang , Li Yong-Zhe , Dong Sheng-Yong , Chen Zong-Tao , Gao Xiang-Yang , Zhang Han , Huang Gang , Xu Yang
Published: December 2020

Background

The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an unprecedented health crisis. The most common chronic illness among patients infected with SARS-CoV-2 is hypertension. Immune dysregulation plays an important role in SARS-CoV-2 infection and in the development of hypertension; however, the dynamic immunological characteristics of COVID-19 patients with hypertension remain largely unclear.

Methods

In total, 258 hypertensive patients infected with SARS-CoV-2 were included in this study. CD38+HLA-DR+ and CD38+PD-1+ CD8+ T cells, IFNγ+CD4+ and IFNγ+CD8+ T cells, the titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and SARS-CoV-2 throat viral loads were measured weekly over 4 weeks after the onset of symptoms. Clinical outcomes were also monitored.

Findings

CD4+ T lymphopenia was observed in 100% of the severe and critical cases. Compared with the surviving patients, the patients with fatal outcomes exhibited high and prolonged expression of CD38+HLA-DR+ and CD38+PD-1+ on CD8+ T cells, low expression of SARS-CoV-2-specific IFNγ+CD4+ and IFNγ+CD8+ T cells, low titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and high SARS-CoV-2 viral load during the illness. In the surviving patients, the viral load was significantly inversely correlated with SARS-CoV-2-specific IFNγ+CD8+and IFNγ+CD4+ T cells, IgG, IgM, and IgA.

Interpretation

T lymphopenia is common in critical or severe COVID-19 cases with hypertension. Prolonged activation and exhaustion of CD8+ T cells were associated with severe disease. The delayed SARS-CoV-2-specific antibody responses may be insufficient for overcoming severe SARS-CoV-2 infection in the absence of SARS-CoV-2-specific cellular responses.
3D Tumor Models and Their Use for the Testing of Immunotherapies
Authors: Boucherit Nicolas , Gorvel Laurent , Olive Daniel
Published: December 2020

Over the past decade, immunotherapy has become a powerful and evident tool in the fight against cancers. Notably, the rise of checkpoint blockade using monoclonal antibodies (anti-CTLA4, anti-PD1) to avoid interaction between inhibitory molecules allowed the betterment of patient care. Indeed, immunotherapies led to increased overall survival in forms of cutaneous melanoma or lung cancer. However, the percentage of patients responding varies from 20 to 40% depending on the type of cancer and on the expression of the target molecules by the tumor. This is due to the tumor microenvironment which allows the acquisition of resistance mechanisms to immunotherapies by tumor cells. These are closely linked to the architecture and cellular composition of the tumor microenvironment. This one acts on different parameters such as the immune cells infiltrate its composition and therefore, favors the recruitment of immunosuppressive cells as well as the tumor expression of checkpoint inhibitors such as Programmed Death Ligand-1 (PD-L1). Therefore, the analysis and modeling of the complexity of the microenvironment is an important parameter to consider, not only in the search for new therapies but also for the identification and stratification of patients likely to respond to immunotherapy. This is why the use of 3D culture models, reflecting the architecture and cellular composition of a tumor, is essential in immuno-oncology studies. Nowadays, there are several 3-D culture methods such as spheroids and organoids, which are applicable to immuno-oncology. In this review we evaluate 3D culture models as tools for the development of treatments in the field of immuno-oncology.
Paving the Way Towards Universal Chimeric Antigen Receptor Therapy in Cancer Treatment: Current Landscape and Progress
Authors: Zhang Yixi , Li Pan , Fang Hongyu , Wang Guocan , Zeng Xun
Published: December 2020

Chimeric antigen receptor (CAR) therapy has been proved effective in a stream of clinical trials, especially in hematologic malignancies. However, current CAR therapy is highly personalized as cells used are derived from patients themselves, which can be costly, time-consuming, and sometimes fails to achieve optimal therapeutic results due to poor quality/quantity of patient-derived cells. On the contrary, universal CAR therapy, which is based on healthy individuals’ cells, circumvents several limitations of current autologous CAR therapy. To achieve the universality of CAR therapy, the allogeneic cell transplantation related issues, such as graft-versus-host disease (GVHD) and host-versus-graft activities (HVGA), must be addressed. In this review, we focus on current progress regarding GVHD and HVGA in the universal CAR therapy, followed by a universal CAR design that may be applied to allogeneic cells and a summary of key clinical trials in this field. This review may provide valuable insights into the future design of universal CAR products.
Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement
Authors: Ohishi Yuta , Ammann Sandra , Ziaee Vahid , Strege Katharina , Groß Miriam , Amos Carla Vazquez , Shahrooei Mohammad , Ashournia Parisa , Razaghian Anahita , Griffiths Gillian M. , Ehl Stephan , Fukuda Mitsunori , Parvaneh Nima
Published: December 2020

Griscelli syndrome type 2 (GS-2) is an inborn error of immunity characterized by partial albinism and episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused by RAB27A mutations that encode RAB27A, a member of the Rab GTPase family. RAB27A is expressed in many tissues and regulates vesicular transport and organelle dynamics. Occasionally, GS-2 patients with RAB27A mutation display normal pigmentation. The study of such variants provides the opportunity to map distinct binding sites for tissue-specific effectors on RAB27A. Here we present a new case of GS-2 without albinism (GS-2 sine albinism) caused by a novel missense mutation (Val143Ala) in the RAB27A and characterize its functional cellular consequences. Using pertinent animal cell lines, the Val143Ala mutation impairs both the RAB27A–SLP2-A interaction and RAB27A–MUNC13-4 interaction, but it does not affect the RAB27A–melanophilin (MLPH)/SLAC2-A interaction that is crucial for skin and hair pigmentation. We conclude that disruption of the RAB27A–MUNC13-4 interaction in cytotoxic lymphocytes leads to the HLH predisposition of the GS-2 patient with the Val143Ala mutation. Finally, we include a review of GS-2 sine albinism cases reported in the literature, summarizing their genetic and clinical characteristics.