bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Insights Into Sterol Uptake and Intracellular Cholesterol Trafficking During Eimeria bovis Macromeront Formation
Authors: Silva Liliana M. R. , Velásquez Zahady D. , López-Osorio Sara , Hermosilla Carlos , Taubert Anja
Published: February 2022

Apicomplexan parasites are considered as defective in cholesterol synthesis. Consequently, they need to scavenge cholesterol from the host cell by either enhancing the uptake of extracellular cholesterol sources or by upregulating host cellular de-novo biosynthesis. Given that Eimeria bovis macromeront formation in bovine lymphatic endothelial host cells in vivo is a highly cholesterol-demanding process, we here examined host parasite interactions based on host cellular uptake of different low-density lipoprotein (LDL) types, i.e., of non-modified (LDL), oxidized (oxLDL), and acetylated LDL (acLDL). Furthermore, the expression of lipoprotein-oxidized receptor 1 (LOX-1), which mediates acLDL and oxLDL internalization, was monitored throughout first merogony, in vitro and ex vivo. Moreover, the effects of inhibitors blocking exogenous sterol uptake or intracellular transport were studied during E. bovis macromeront formation in vitro. Hence, E. bovis-infected primary bovine umbilical vein endothelial cells (BUVEC) were treated with inhibitors of sterol uptake (ezetimibe, poly-C, poly-I, sucrose) and of intracellular sterol transport and release from endosomes (progesterone, U18666A). As a read-out system, the size and number of macromeronts as well as merozoite I production were estimated. Overall, the internalization of all LDL modifications (LDL, oxLDL, acLDL) was observed in E. bovis-infected BUVEC but to different extents. Supplementation with oxLDL and acLDL at lower concentrations (5 and 10 µg/ml, respectively) resulted in a slight increase of both macromeront numbers and size; however, at higher concentrations (25–50 µg/ml), merozoite I production was diminished. LOX-1 expression was enhanced in E. bovis-infected BUVEC, especially toward the end of merogony. As an interesting finding, ezetimibe treatments led to a highly significant blockage of macromeront development and merozoite I production confirming the relevance of sterol uptake for intracellular parasite development. Less prominent effects were induced by non-specific inhibition of LDL internalization via sucrose, poly-I, and poly-C. In addition, blockage of cholesterol transport via progesterone and U18666A treatments resulted in significant inhibition of parasite development. Overall, current data underline the relevance of exogenous sterol uptake and intracellular cholesterol transport for adequate E. bovis macromeront development, unfolding new perspectives for novel drug targets against E. bovis.
The Seasonally Altered Atmosphere Moisture Circulations With Rainfall and Rainfall Isotopes in Southwest China
Authors: Zhao Jingyao , Tan Liangcheng , Li Dong , Pérez-Mejías Carlos , Dong Xiyu , Wang Jian , Zhang Haiwei , Cheng Hai
Published: February 2022

To interpret the climatic signals of precipitation/speleothem δ18O, it is critical to identify the importance of the factors affecting the precipitation δ18O. This study presents new stable isotope data for precipitation δ18O and δD in the site of Shenqi cave, southwest China, from November-2015 to October-2016 (the “Super-El Niño” event), to investigate the regional-scale climate forcing on precipitation δ18O. The precipitation δ18O, δD and d-excess have an obvious seasonality, relatively low values in the wet season and high in the dry season. The further analysis of seasonally altered LMWL and moisture circulations suggested that changes in atmosphere moisture circulations would be the key factor underlying the precipitation/speleothem δ18O fluctuations in our study area at least on seasonal timescales. Combined with the seasonal-monthly variations of the IsoGSM δ18O, GPCP/CRU rainfall and NCEP/NCAR moisture fluxes, we detected that the super-El Niño of 2016 have changed the distributions of monthly rainfall in wet season through the Western Pacific Subtropical High, but not mainly the precipitation isotopic compositions and moisture circulations in our study area.
Numerical Analysis of Zipper Fracturing Using a Non-Planar 3D Fracture Model
Authors: Wang Zhen , Yang Lifeng , Gao Rui , Xu Guanshui , Liu Zhe , Mo Shaoyuan , Fan Meng , Wang Xin
Published: February 2022

Zipper fracturing has become one of the routine reservoir stimulation methods for developing unconventional resources such as shale oil and gas. A non-planar 3D fracture propagation model is used to study the fracture propagation behavior of zipper fracturing. The effects of stage time lag, staggered perforation cluster spacing, and horizontal principal stress contrast on the fracture geometry are analyzed through numerical simulation. The simulation results show that increasing the stage time lag can increase the fracture length and improve inter-well stimulation. For the formation with higher horizontal principal stress contrast, the staggered perforation cluster spacing has a minimum effect on the fracture configuration of zipper fracturing. For the formation with lower horizontal principal stress contrast, the fractures follow the curved paths and intersect with each other, which potentially has adverse effects on the stimulation of the subsequent stages.
Nanoscale Pore Characteristics of the Lower Permian Shanxi Formation Transitional Facies Shale, Eastern Ordos Basin, North China
Authors: Wang Zhanlei , Guo Bingzheng , Jiang Chan , Qi Lin , Jiang Yuqiang , Gu Yifan , Fu Yonghong , Liang Demin
Published: February 2022

The Lower Permian Shanxi Formation in the Eastern Ordos Basin is a set of transitional facies shale, and it is also a key target for shale gas exploration in China. Based on lithofacies classification by X-ray diffraction and kerogen type identification, nanoscale reservoir space, pore volume, pore size distribution, surface area, and fractal characterization were studied using comprehensive methods including N2 and CO2 adsorption, mercury injection capillary pressure, field emission-scanning electron microscopy (FE-SEM), and nuclear magnetic resonance. The results indicate that Shanxi Formation shale can be subdivided into five types of lithofacies: clayey shale (lithofacies I), siliceous clayey shale (lithofacies II), siliceous shale (lithofacies IV), calcareous siliceous shale (lithofacies V), and siliceous calcareous shale (lithofacies VI). Lithofacies V and lithofacies VI are the best lithofacies in terms of organic pore morphology, connectivity, and development degree, followed by lithofacies II. Inorganic pores and microfractures are well developed in all lithofacies. The majority of pores in lithofacies I comprise organic mesopores, but pore volume is contributed by a few inorganic macropores. The pore types and pore volume contributors of lithofacies II are organic macropores. The pore size distribution of lithofacies IV is very similar to that of lithofacies I. The pore size distribution of lithofacies V shows typical bimodal characteristics. It is suggested that the inorganic pores of lithofacies V are mainly macropores, which have the greatest contribution to pore volume, followed by organic mesopores. Total organic carbon (TOC) and thermal maturity do not present obvious controls on pore structure. Vitrinite is the main kerogen type in lithofacies II and IV, and this is associated with disfavored morphology, low connectivity, and poor development degree of organic pores. In contrast, sapropelinite is observed in other shale lithofacies, and it is suggested to be an effective kerogen type that contributes to better development of organic pores.
Research Into improved Distance Learning Using VR Technology
Authors: Li Pengfei , Fang Zelong , Jiang Tan
Published: February 2022

Practical skill-based education requires exemplary face-to-face operational teaching, and VR can enhance online distance learning, facilitating an alternative form of “face-to-face” teaching, which results in better teacher–student communication and learner self-efficacy. It also constitutes as a useful substitute for in-person teaching, and it also has a positive impact on learning effectiveness. In this study, a mixed-method approach was used, which utilized the following methodologies: a combination of quantitative and qualitative measures, document collection, case and comparative analysis, and VR teaching that utilizes “You, Calligrapher” as a survey tool. Teachers and students of art were selected, who then used an educational VR-based calligraphy game application for teaching activities. We investigated the impact of virtual time, space, and technical availability on learners’ understanding, imagination, and interactivity in VR education, and then we evaluated the positive impact via learner feedback. Research tools that we utilized consist of comprehension, imagination, and how feedback motivation scales with effective learning; we have also used Chinese calligraphy performance tests. The SPSS statistical analysis software was used for related statistical processing, and α was set to 0.05. The results of this study indicated that Chinese calligraphy studies in VR time and space affect students’ understanding and imagination but not their operational abilities. According to our research, a fundamental difference between traditional and modern teaching methods is a shift toward the use of VR (and the internet) in education. Therefore, the focus of this study is on understanding the impact on practical skills during distance learning and investing the impacts in order to form an effective approach to the use of VR in education.
Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis
Authors: Merz Karla E. , Tunduguru Ragadeepthi , Ahn Miwon , Salunkhe Vishal A. , Veluthakal Rajakrishnan , Hwang Jinhee , Bhattacharya Supriyo , McCown Erika M. , Garcia Pablo A. , Zhou Chunxue , Oh Eunjin , Yoder Stephanie M. , Elmendorf Jeffrey S. , Thurmond Debbie C.
Published: February 2022

Skeletal muscle accounts for ~80% of insulin-stimulated glucose uptake. The Group I p21–activated kinase 1 (PAK1) is required for the non-canonical insulin-stimulated GLUT4 vesicle translocation in skeletal muscle cells. We found that the abundances of PAK1 protein and its downstream effector in muscle, ARPC1B, are significantly reduced in the skeletal muscle of humans with type 2 diabetes, compared to the non-diabetic controls, making skeletal muscle PAK1 a candidate regulator of glucose homeostasis. Although whole-body PAK1 knockout mice exhibit glucose intolerance and are insulin resistant, the contribution of skeletal muscle PAK1 in particular was unknown. As such, we developed inducible skeletal muscle-specific PAK1 knockout (skmPAK1-iKO) and overexpression (skmPAK1-iOE) mouse models to evaluate the role of PAK1 in skeletal muscle insulin sensitivity and glucose homeostasis. Using intraperitoneal glucose tolerance and insulin tolerance testing, we found that skeletal muscle PAK1 is required for maintaining whole body glucose homeostasis. Moreover, PAK1 enrichment in GLUT4-myc-L6 myoblasts preserves normal insulin-stimulated GLUT4 translocation under insulin resistance conditions. Unexpectedly, skmPAK1-iKO also showed aberrant plasma insulin levels following a glucose challenge. By applying conditioned media from PAK1-enriched myotubes or myoblasts to β-cells in culture, we established that a muscle-derived circulating factor(s) could enhance β-cell function. Taken together, these data suggest that PAK1 levels in the skeletal muscle can regulate not only skeletal muscle insulin sensitivity, but can also engage in tissue crosstalk with pancreatic β-cells, unveiling a new molecular mechanism by which PAK1 regulates whole-body glucose homeostasis.
Effect of Grazing Exclusion and Rotational Grazing on Soil Aggregate Stability in Typical Grasslands in Inner Mongolia, China
Authors: Dong Lei , Zheng Ying , Martinsen Vegard , Liang Cunzhu , Mulder Jan
Published: February 2022

Soil aggregate is extremely important for soil health and sustainable land management. Overgrazing has caused serious degeneration of grassland in the past decades and how to restore the degraded soil through grazing management is urgently needed. In this research, we investigated effects of long-term grazing exclusion and short-term rotational grazing with different grazing intensities on aggregate stability in the upper 10 cm of soil at two grazing sites in Xilinhot, Inner Mongolia. Treatments included long-term (34 years) exclusion, moderate-term (21 years) exclusion, and continuous grazing at adjacent reference plots. In addition, effects of rotational grazing under different grazing intensity [i.e., no grazing (0 days/month), light grazing (3 days/month), moderate grazing (6 days/month) and high grazing (12 days/month)] were investigated after 5 years. Stability of aggregate fractions were determined using wet sieving. Our results showed that the stable aggregates fraction were significantly increased under grazing exclusion for both fine (0.25–1 mm) and coarse (1–2 mm) size fractions. At the rotational grazing site, stability of fine aggregates was significantly enhanced under grazing compared with no grazing, while there was little influence on stability of coarse aggregates. Our results showed that grazing exclusion significantly increased soil aggregate stability and the peak appeared in moderate-term exclusion, meanwhile, rotational grazing had little influence on aggregate stability. We suggest that rotational grazing rather than long-term grazing exclusion is a better way for soil aggregate stability and soil health, and current grazing prohibition policies may need to be adjusted.
A Burst of Numt Insertion in the Dasyuridae Family During Marsupial Evolution
Authors: Hazkani-Covo Einat
Published: February 2022

Nuclear pseudogenes of mitochondrial origin (numts) are common in all eukaryotes. Our previous scan of numts in sequenced nuclear genomes suggested that the highest numt content currently known in animals is that in the gray short-tailed opossum. The present work sought to determine numt content in marsupials and to compare it to those in placental and monothematic mammals as well as in non-mammalian vertebrates. To achieve this, 70 vertebrate species with available nuclear and mitochondrial genomes were scanned for numt content. An extreme numt content was found in the Dasyuridae, with 3,450 in Sarcophilus harrisii (1,955 kb) and 2,813 in Antechinus flavipes (847 kb). The evolutionarily closest species analyzed, the extinct Thylacinus cynocephalus belonging to the Thylacindae family, had only 435 numts (238 kb). These two Dasyuridae genomes featured the highest numt content identified in animals to date. A phylogenetic analysis of numts longer than 300 bp, using a Diprotodonita mitochondrial tree, indicated a burst of numt insertion that began before the divergence of the Dasyurini and Phascogalini, reaching a peak in the early evolution of the two tribes. No comparable increase was found in the early divergent species T. cynocephalus. Divergence of the Dasyuridae tribes has been previously dated to shortly after the Miocene climate transition, characterized by a rapid temperature decline. Interestingly, deviation from optimal growth temperature is one of the environmental factors reported to increase numt insertions in a laboratory setting.
Discovering Copy Number Variation in Dual-Purpose XinJiang Brown Cattle
Authors: Zhou Jinghang , Liu Liyuan , Reynolds Edwardo , Huang Xixia , Garrick Dorian , Shi Yuangang
Published: February 2022

Copy number variants (CNVs), which are a class of structural variant, can be important in relating genomic variation to phenotype. The primary aims of this study were to discover the common CNV regions (CNVRs) in the dual-purpose XinJiang-Brown cattle population and to detect differences between CNVs inferred using the ARS-UCD 1.2 (ARS) or the UMD 3.1 (UMD) genome assemblies based on the 150K SNP (Single Nucleotide Polymorphisms) Chip. PennCNV and CNVPartition methods were applied to calculate the deviation of the standardized signal intensity of SNPs markers to detect CNV status. Following the discovery of CNVs, we used the R package HandyCNV to generate and visualize CNVRs, compare CNVs and CNVRs between genome assemblies, and identify consensus genes using annotation resources. We identified 38 consensus CNVRs using the ARS assembly with 1.95% whole genome coverage, and 33 consensus CNVRs using the UMD assembly with 1.46% whole genome coverage using PennCNV and CNVPartition. We identified 37 genes that intersected 13 common CNVs (>5% frequency), these included functionally interesting genes such as GBP4 for which an increased copy number has been negatively associated with cattle stature, and the BoLA gene family which has been linked to the immune response and adaption of cattle. The ARS map file of the GGP Bovine 150K Bead Chip maps the genomic position of more SNPs with increased accuracy compared to the UMD map file. Comparison of the CNVRs identified between the two reference assemblies suggests the newly released ARS reference assembly is better for CNV detection. In spite of this, different CNV detection methods can complement each other to generate a larger number of CNVRs than using a single approach and can highlight more genes of interest.
Healthcare Workers’ Knowledge and Resource Availability for Care of Sickle Cell Disease in Dar es Salaam, Tanzania
Authors: Jonathan Agnes , Tutuba Hilda , Lloyd William , Ndunguru Joyce , Makani Julie , Ruggajo Paschal , Minja Irene K. , Balandya Emmanuel
Published: February 2022

Background: Sickle cell disease (SCD) is a global public health priority due to its high morbidity and mortality. In Tanzania, SCD accounts for 7% of under-five mortality. Cost-effective interventions such as early diagnosis and linkage to care have been shown to prevent 70% of deaths but require knowledge among healthcare workers and availability of resources at health facilities. In Tanzania, data on these critical determinants are currently lacking.

Objective: To assess healthcare workers’ knowledge and resource availability for care of SCD at health facilities in Dar es Salaam, Tanzania.

Methodology: A facility-based cross-sectional study was conducted between December 2020 and February 2021 among 490 nurses and clinicians at Regional Referral Hospitals (Temeke, Amana, and Mwananyamala) and Muhimbili National Hospital in Dar es Salaam, Tanzania. Data were collected using a pre-tested structured questionnaire consisting of 13 knowledge questions (scored good knowledge if correct response in >7) and an inventory check list to record available resources. Pearson’s χ2 was used to determine the association between level of knowledge and demographic factors. Multivariate logistic regression was used to ascertain the strength of associations. A two-tailed p-value <0.05 was considered to be statistically significant.

Results: Of the 490 participants (median age 28 years [IQR = 26–35]), only 25.1% had good knowledge on SCD. The odds of good knowledge was 82% lower in nurses than clinicians (AOR = 0.177; 95% CI: 0.090, 0.349; p < 0.001); 95% lower in diploma than Master’s degree holders (AOR = 0.049; 95% CI: 0.008, 0.300; p = 0.001) and 4.6 times higher in those with 5–9 years than ≥10 years of experience (AOR = 4.564; 95% CI: 1.341, 15.525; p = 0.015). The regional-level hospitals lacked diagnostic tests and hydroxyurea therapy.

Conclusion: There was general lack of knowledge on SCD among healthcare workers and limited availability of critical resources for the diagnosis and care of SCD, especially at regional-level hospitals. Efforts are needed for their improvement to enhance care to patients, thus reducing the morbidity and mortality due to SCD in Tanzania.
Genetic Insight Into the Insect Resistance in Bread Wheat Exploiting the Untapped Natural Diversity
Authors: Arif Mian Abdur Rehman , Waheed Muhammad Qandeel , Lohwasser Ulrike , Shokat Sajid , Alqudah Ahmad M. , Volkmar Christa , Börner Andreas
Published: February 2022

Climate change is an undeniable threat to sustainable wheat production in the future as an increased temperature will significantly increase grain loss due to the increased number of generations per season of multivoltine species that are detrimental to plants. Among insects, orange wheat blossom midge (OWBM), yellow wheat blossom midge (YWBM), saddle gall midge (SGM), thrips, and frit fly (FF) are important wheat pests in the European environments, which can be managed by the development of resistant cultivars. This involves the identification, confirmation, and incorporation of insect resistance sources into new high-yielding cultivars. We used two diverse and unrelated wheat [winter wheat (WW) and spring wheat (SW)] panels to associate single-nucleotide polymorphism (SNP) markers with the mentioned pests using the tools of association mapping. All in all, a total of 645 and 123 significant associations were detected in WW and SW, respectively, which were confined to 246 quantitative trait loci. Many candidate genes were identified using the BLAST analysis of the sequences of associated SNPs. Some of them are involved in controlling the physical structures of plants such as stomatal immunity and closure, cuticular wax in leaf blade, whereas others are involved in the production of certain enzymes in response to biotic and abiotic stresses. To our knowledge, this is the first detailed investigation that deals with YWBM, SGM, thrips, and FF resistance genetics using the natural variation in wheat. The reported germplasm is also readily available to breeders across the world that can make rational decisions to breed for the pest resilience of their interest by including the resistant genotypes being reported.
Polysialic Acid in the Immune System
Authors: Villanueva-Cabello Tania M. , Gutiérrez-Valenzuela Lya D. , Salinas-Marín Roberta , López-Guerrero Delia V. , Martínez-Duncker Iván
Published: February 2022

Polysialic acid (polySia) is a highly regulated polymer of sialic acid (Sia) with such potent biophysical characteristics that when expressed drastically influences the interaction properties of cells. Although much of what is known of polySia in mammals has been elucidated from the study of its role in the central nervous system (CNS), polySia is also expressed in other tissues, including the immune system where it presents dynamic changes during differentiation, maturation, and activation of different types of immune cells of the innate and adaptive response, being involved in key regulatory mechanisms. At least six polySia protein carriers (CCR7, ESL-1, NCAM, NRP2, ST8Sia 2, and ST8Sia 4) are expressed in different types of immune cells, but there is still much to be explored in regard not only to the regulatory mechanisms that determine their expression and the structure of polySia chains but also to the identification of the cis- and trans- ligands of polySia that establish signaling networks. This review summarizes the current knowledge on polySia in the immune system, addressing its biosynthesis, its tools for identification and structural characterization, and its functional roles and therapeutic implications.
Pre-COVID-19 Immunity to Common Cold Human Coronaviruses Induces a Recall-Type IgG Response to SARS-CoV-2 Antigens Without Cross-Neutralisation
Authors: Miyara Makoto , Saichi Melissa , Sterlin Delphine , Anna François , Marot Stéphane , Mathian Alexis , Atif Mo , Quentric Paul , Mohr Audrey , Claër Laetitia , Parizot Christophe , Dorgham Karim , Yssel Hans , Fadlallah Jehane , Chazal Thibaut , Haroche Julien , Luyt Charles-Edouard , Mayaux Julien , Beurton Alexandra , Benameur Neila , Boutolleau David , Burrel Sonia , de Alba Sophia , Mudumba Sasi , Hockett Rick , Gunn Cary , Charneau Pierre , Calvez Vincent , Marcelin Anne-Geneviève , Combes Alain , Demoule Alexandre , Amoura Zahir , Gorochov Guy
Published: February 2022

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.
Standardization of Workflow and Flow Cytometry Panels for Quantitative Expression Profiling of Surface Antigens on Blood Leukocyte Subsets: An HCDM CDMaps Initiative
Authors: Kužílková Daniela , Puñet-Ortiz Joan , Aui Pei M. , Fernández Javier , Fišer Karel , Engel Pablo , van Zelm Menno C. , Kalina Tomáš
Published: February 2022

Background

The Human Cell Differentiation Molecules (HCDM) organizes Human Leukocyte Differentiation Antigen (HLDA) workshops to test and name clusters of antibodies that react with a specific antigen. These cluster of differentiation (CD) markers have provided the scientific community with validated antibody clones, consistent naming of targets and reproducible identification of leukocyte subsets. Still, quantitative CD marker expression profiles and benchmarking of reagents at the single-cell level are currently lacking.

Objective

To develop a flow cytometric procedure for quantitative expression profiling of surface antigens on blood leukocyte subsets that is standardized across multiple research laboratories.

Methods

A high content framework to evaluate the titration and reactivity of Phycoerythrin (PE)-conjugated monoclonal antibodies (mAbs) was created. Two flow cytometry panels were designed: an innate cell tube for granulocytes, dendritic cells, monocytes, NK cells and innate lymphoid cells (12-color) and an adaptive lymphocyte tube for naive and memory B and T cells, including TCRγδ+, regulatory-T and follicular helper T cells (11-color). The potential of these 2 panels was demonstratedviaexpression profiling of selected CD markers detected by PE-conjugated antibodies and evaluated using 561 nm excitation.

Results

Using automated data annotation and dried backbone reagents, we reached a robust workflow amenable to processing hundreds of measurements in each experiment in a 96-well plate format. The immunophenotyping panels enabled discrimination of 27 leukocyte subsets and quantitative detection of the expression of PE-conjugated CD markers of interest that could quantify protein expression above 400 units of antibody binding capacity. Expression profiling of 4 selected CD markers (CD11b, CD31, CD38, CD40) showed high reproducibility across centers, as well as the capacity to benchmark unique clones directed toward the same CD3 antigen.

Conclusion

We optimized a procedure for quantitative expression profiling of surface antigens on blood leukocyte subsets. The workflow, bioinformatics pipeline and optimized flow panels enable the following: 1) mapping the expression patterns of HLDA-approved mAb clones to CD markers; 2) benchmarking new antibody clones to established CD markers; 3) defining new clusters of differentiation in future HLDA workshops.
A Comprehensive Monitoring and Assessment System for Multiple Fisheries Resources in the Northwest Pacific Based on Satellite Remote Sensing Technology
Authors: Tian Hao , Liu Yang , Tian Yongjun , Alabia Irene D. , Qin Yuanzhe , Sun He , Li Jianchao , Ma Shuyang , Saitoh Sei-Ichi
Published: February 2022

Monitoring the dynamics of ocean-going fishing vessels is essential for fisheries stock assessment and management. In this paper, coupled fishery and remote sensing methods were applied to propose a satellite-based fishery resource monitoring and assessment system (SFRMAS) that supported chub mackerel (Scomber japonicus), Pacific saury (Cololabis saira) and neon flying squid (Ommastrephes bartramii) fishing activities in the northwest Pacific. A multispecies fishing vessel database was generated in the SFRMAS using visible infrared imaging radiometer suite day/night band (VIIRS/DNB) images, automatic identification system (AIS) data and multimarine remote sensing resources. The results showed that the VIIRS/DNB vessel detection (VVD) and AIS vessel detection approaches improved the extraction accuracy of multispecies fishing vessels. A high productivity area with a higher chlorophyll a concentration had the most concentrated distribution of mackerel vessels. The widest longitudinal migrations of the neon flying squid and the latitudinal ranges of Pacific saury were highly related to sea surface temperature (SST), which was well captured by the movement of the fishing vessels. In the SFRMAS, the accuracy of detected multispecies fishing days and fishing catches was mostly between 60 and 90%, which can provide data support for fisheries stock assessment and management.
Ocean Acidification Effect on the Iron-Gallic Acid Redox Interaction in Seawater
Authors: Pérez-Almeida Norma , González Aridane G. , Santana-Casiano J. Magdalena , González-Dávila Melchor
Published: February 2022

Ocean acidification impacts the iron (Fe) biogeochemistry both by its redox and its complexation reactions. This has a direct effect on the ecosystems due to Fe being an essential micronutrient. Polyphenols exudated by marine microorganisms can complex Fe(III), modifying the Fe(II) oxidation rates as well as promoting the reduction of Fe(III) to Fe(II) in seawater. The effect of the polyphenol gallic acid (GA; 3,4,5-trihydroxy benzoic acid) on the oxidation and reduction of Fe was studied. The Fe(II) oxidation rate constant decreased, increasing the permanence of Fe(II) in solutions at nM levels. At pH = 8.0 and in the absence of gallic acid, 69.3% of the initial Fe(II) was oxidized after 10 min. With 100 nM of gallic acid (ratio 4:1 GA:Fe), and after 30 min, 37.5% of the initial Fe(II) was oxidized. Fe(III) is reduced to Fe(II) by gallic acid in a process that depends on the pH and composition of solution, being faster as pH decreases. At pH > 7.00, the Fe(III) reduction rate constant in seawater was lower than in NaCl solutions, being the difference at pH 8.0 of 1.577 × 10–5 s–1. Moreover, the change of the Fe(III) rate constant with pH, within the studied range, was higher in seawater (slope = 0.91) than in NaCl solutions (slope = 0.46). The Fe(III) reduction rate constant increased with increasing ligand concentration, being the effect higher at pH 7.0 [k′ = 1.078 × 10–4 s–1; (GA) = 250 nM] compared with that at pH 8.0 [k′ = 3.407 × 10–5 s–1; (GA) = 250 nM]. Accordingly, gallic acid reduces Fe(III) to Fe(II) in seawater, making possible the presence of Fe(II) for longer periods and favoring its bioavailability.
Glucocorticoids Inhibit EGFR Signaling Activation in Podocytes in Anti-GBM Crescentic Glomerulonephritis
Authors: Wu Xiaomei , Ren Lu , Yang Qianqian , Song Hui , Tang Qiaoli , Zhang Mingchao , Zhang Jiong , Tang Zheng , Shi Shaolin
Published: February 2022

Glucocorticoids are commonly used to treat anti-GBM crescentic glomerulonephritis, however, the mechanism underlying its therapeutic effectiveness is not completely understood. Since podocyte EGFR/STAT3 signaling is known to mediate the development of anti-GBM glomerulonephritis, we investigated the effect of glucocorticoids on EGFR/STAT3 signaling in podocytes. We found that the levels of phosphorylated (activated) EGFR and STAT3 in podocytes were markedly elevated in anti-GBM patients without glucocorticoids treatment, but were normalized in patients with glucocorticoids treatment. In a rat model of anti-GBM glomerulonephritis, glucocorticoids treatment significantly attenuated the proteinuria, crescent formation, parietal epithelial cell (PEC) activation and proliferation, accompanied by elimination of podocyte EGFR/STAT3 signaling activation. In cultured podocytes, glucocorticoids were found to inhibit HB-EGF-induced EGFR and STAT3 activation. The conditioned medium from podocytes treated with HB-EGF in the absence but not presence of glucocorticoids was capable of activating Notch signaling (which is known to be involved in PEC proliferation and crescent formation) and enhancing proliferative activity in primary PECs, suggesting that glucocorticoids prevent podocytes from producing secreted factors that cause PEC proliferation and crescent formation. Furthermore, we found that glucocorticoids can downregulate the expression of EGFR ligands, EGF and HB-EGF, while upregulate the expression of EGFR inhibitor, Gene 33, explaining how glucocorticoids suppress EGFR signaling. Taken together, glucocorticoids exert therapeutic effect on anti-GBM crescentic glomerulonephritis through inhibiting podocyte EGFR/STAT3 signaling and the downstream pathway that leads to PEC proliferation and crescent formation.
The Impact of Breathing Hypoxic Gas and Oxygen on Pulmonary Hemodynamics in Patients With Pulmonary Hypertension
Authors: Carta Arcangelo F. , Lichtblau Mona , Berlier Charlotte , Saxer Stéphanie , Schneider Simon R. , Schwarz Esther I. , Furian Michael , Bloch Konrad E. , Ulrich Silvia
Published: February 2022

Background

Pure oxygen breathing (hyperoxia) may improve hemodynamics in patients with pulmonary hypertension (PH) and allows to calculate right-to-left shunt fraction (Qs/Qt), whereas breathing normobaric hypoxia may accelerate hypoxic pulmonary vasoconstriction (HPV). This study investigates how hyperoxia and hypoxia affect mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PH and whether Qs/Qt influences the changes of mPAP and PVR.

Study Design and Methods

Adults with pulmonary arterial or chronic thromboembolic PH (PAH/CTEPH) underwent repetitive hemodynamic and blood gas measurements during right heart catheterization (RHC) under normoxia [fractions of inspiratory oxygen (FiO2) 0.21], hypoxia (FiO2 0.15), and hyperoxia (FiO2 1.0) for at least 10 min.

Results

We included 149 patients (79/70 PAH/CTEPH, 59% women, mean ± SD 60 ± 17 years). Multivariable regressions (mean change, CI) showed that hypoxia did not affect mPAP and cardiac index, but increased PVR [0.4 (0.1–0.7) WU, p = 0.021] due to decreased pulmonary artery wedge pressure [−0.54 (−0.92 to −0.162), p = 0.005]. Hyperoxia significantly decreased mPAP [−4.4 (−5.5 to −3.3) mmHg, p < 0.001] and PVR [−0.4 (−0.7 to −0.1) WU, p = 0.006] compared with normoxia. The Qs/Qt (14 ± 6%) was >10 in 75% of subjects but changes of mPAP and PVR under hyperoxia and hypoxia were independent of Qs/Qt.

Conclusion

Acute exposure to hypoxia did not relevantly alter pulmonary hemodynamics indicating a blunted HPV-response in PH. In contrast, hyperoxia remarkably reduced mPAP and PVR, indicating a preserved vasodilator response to oxygen and possibly supporting the oxygen therapy in patients with PH. A high proportion of patients with PH showed increased Qs/Qt, which, however, was not associated with changes in pulmonary hemodynamics in response to changes in FiO2.
A Three-Dimensional Organoid Model of Primary Breast Cancer to Investigate the Effects of Oncolytic Virotherapy
Authors: Carter Mary E. , Hartkopf Andreas D. , Wagner Anna , Volmer Léa L. , Brucker Sara Y. , Berchtold Susanne , Lauer Ulrich M. , Koch André
Published: February 2022

Background:Although several oncolytic viruses have already been tested in early-stage clinical studies of breast cancer, there is still an urgent need to develop patient-derived experimental systems that mimic the response of breast cancer to oncolytic agents in preparation of testing different oncolytic viruses in clinical trials. We addressed this need by developing a protocol to study the effects of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue.

Methods:We used an established three-dimensional organoid model derived from tissue of 10 patients with primary breast cancer. We developed an experimental protocol for infecting organoid cultures with oncolytic viruses and compared the oncolytic effects of a measles vaccine virus (MeV) and a vaccinia virus (GLV) genetically engineered to express either green fluorescent protein (MeV-GFP) and red fluorescent protein (GLV-0b347), respectively, or a suicide gene encoding a fusion of cytosine deaminase with uracil phosphoribosyltransferase (MeV-SCD and GLV-1h94, respectively), thereby enabling enzymatic conversion of the prodrug 5-fluorocytosine (5-FC) into cytotoxic compounds 5-fluorouracil (5-FU) and 5-fluorouridine monophosphate (5-FUMP).

Results:The method demonstrated that all oncolytic viruses significantly inhibited cell viability in organoid cultures derived from breast cancer tissue. The oncolytic effects of the oncolytic viruses expressing suicide genes (MeV-SCD and GLV-1h94) were further enhanced by virus-triggered conversion of the prodrug 5-FC to toxic 5-FU and toxic 5-FUMP.

Conclusions:We were able to develop a protocol to assess the effects of two different types of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. The greatest oncolytic effects were observed when the oncolytic viruses were engineered to express a suicide gene (MeV-SCD and GLV-1h94) in the presence of the prodrug 5-FC. The model therefore provides a promisingin vitromethod to help further testing and engineering of new generations of virotherapeutic vectors forin vivouse.
Inferring Retinal Degeneration-Related Genes Based on Xgboost
Authors: Xia Yujie , Li Xiaojie , Chen Xinlin , Lu Changjin , Yu Xiaoyi
Published: February 2022

Retinal Degeneration (RD) is an inherited retinal disease characterized by degeneration of rods and cones photoreceptor cells and degeneration of retinal pigment epithelial cells. The age of onset and disease progression of RD are related to genes and environment. At present, research has discovered five genes closely related to RD. They are RHO, PDE6B, MERTK, RLBP1, RPGR, and researchers have developed corresponding gene therapy methods. Gene therapy uses vectors to transfer therapeutic genes, genetically modify target cells, and correct or replace disease-causing RD genes. Therefore, identifying the pathogenic genes of RD will play an important role in the development of treatment methods for the disease. However, the traditional methods of identifying RD-related genes are mostly based on animal experiments, and currently only a small number of RD-related genes have been identified. With the increase of biological data, Xgboost is purposed in this article to identify RP-related genes. Xgboost adds a regular term to control the complexity of the model, hence using Xgboost to find out true RD-related genes from complex and massive genes is suitable. The problem of overfitting can be avoided to some extent. To verify the power of Xgboost to identify RD-related genes, we did 10-cross validation and compared with three traditional methods: Random Forest, Back Propagation network, Support Vector Machine. The accuracy of Xgboost is 99.13% and AUC is much higher than other three methods. Therefore, this article can provide technical support for efficient identification of RD-related genes and help researchers have a deeper the understanding of the genetic characteristics of RD.
The Effects of Rosiglitazone on Task Specific Anxiety-Like Behavior and Novelty Seeking in a Model of Chronic Adolescent Unpredictable Stress
Authors: Sexton Hannah G. , Olszewski Nathan A. , Risher Mary-Louise
Published: February 2022

Adolescence is characterized as a period of increased social behavior, risk taking, and novelty seeking, partly due to ongoing maturation in critical brain areas and the hypothalamic-pituitary-adrenal (HPA) negative-feedback system. During this period there is heightened vulnerability to stress that can drive neuro-immune-endocrine remodeling, resulting in the emergence of maladaptive behaviors that increase susceptibility to alcohol and substance abuse. Here we used a rat model to investigate the impact of chronic adolescent unpredictable stress on a battery of behavioral measures to assess anxiety, novelty seeking, risk taking, depression, and voluntary ethanol consumption while determining whether the PPARγ agonist rosiglitazone can attenuate these effects. Adolescent female rats that experienced stress showed increased risk taking behavior and novelty seeking behavior with no change in ethanol consumption. The administration of rosiglitazone during stress induction attenuated stress-induced cortisol elevation, normalized risk taking behavior in a model anxiety, and attenuated novelty seeking in a task-specific manner. Depressive-like behavior was not impacted by adolescent unpredictable stress or the administration of rosiglitazone. The results from this study demonstrate that exposure to unpredictable stress during adolescence increases the prevalence of maladaptive behaviors that are known to increase susceptibility to alcohol and substance abuse, and that rosiglitazone may be an effective therapeutic to attenuate the emergence of select risk taking and novelty seeking behaviors in females.
MPPTM: A Bio-Inspired Approach for Online Path Planning and High-Accuracy Tracking of UAVs
Authors: Yi Xin , Zhu Anmin , Yang S. X.
Published: February 2022

The path planning and tracking problem of the multi-robot system (MRS) has always been a research hotspot and applied in various fields. In this article, a novel multi-robot path planning and tracking model (MPPTM) is proposed, which can carry out online path planning and tracking problem for multiple mobile robots. It considers many issues during this process, such as collision avoidance, and robot failure. The proposed approach consists of three parts: a neural dynamic path planner, a hyperbolic tangent path optimizer, and an error-driven path tracker. Assisted by Ultra-wideband positioning system, the proposed MPPTM is a low-cost solution for online path planning and high-accurate tracking of MRS in practical environments. In the proposed MPPTM, the proposed path planner has good time performance, and the proposed path optimizer improves tracking accuracy. The effectiveness, feasibility, and better performance of the proposed model are demonstrated by real experiments and comparative simulations.
Feasibility of Telemedical HINTS (Head Impulse-Nystagmus-Test of Skew) Evaluation in Patients With Acute Dizziness or Vertigo in the Emergency Department of Primary Care Hospitals
Authors: von Martial Rascha , Leinweber Christina , Hubert Nikolai , Rambold Holger , Haberl Roman Ludwig , Hubert Gordian Jan , Müller-Barna Peter
Published: February 2022

Background

Acute dizziness, vertigo and imbalance are common symptoms in emergency departments. Stroke needs to be distinguished from vestibular diseases. A battery of three clinical bedside tests (HINTS: Head Impulse Test, Nystagmus, Test of Skew) has been shown to detect stroke as underlying cause with high reliability, but implementation is challenging in primary care hospitals. Aim of this study is to prove the feasibility of a telemedical HINTS examinationviaa remotely controlled videooculography (VOG) system.

Methods

The existing video system of our telestroke network TEMPiS (Telemedic Project for Integrative Stroke Care) was expanded through a VOG system. This feature enables the remote teleneurologist to assess a telemedical HINTS examination based on inspection of eye movements and quantitative video head impulse test (vHIT) evaluation. ED doctors in 11 spoke hospitals were trained in performing vHIT, nystagmus detection and alternating cover test. Patients with first time acute dizziness, vertigo or imbalance, whether ongoing or resolved, presented to the teleneurologist were included in the analysis, as long as no focal neurological deficit according to the standard teleneurological examination or obvious internal medicine cause was present and a fully trained team was available. Primary outcome was defined as the feasibility of the telemedical HINTS examination.

Results

From 01.06.2019 to 31.03.2020, 81 consecutive patients were included. In 72 (88.9%) cases the telemedical HINTS examination was performed. The complete telemedical HINTS examination was feasible in 46 cases (63.9%), nystagmus detection in all cases (100%) and alternating covert test in 70 cases (97.2%). The vHIT was recorded and interpretable in 47 cases (65.3%). Results of the examination with the VOG system yielded clear results in 21 cases (45.7%) with 14 central and 7 peripheral lesions. The main reason for incomplete examination was the insufficient generation of head impulses.

Conclusion

In our analysis the telemedical HINTS examination within a telestroke network was feasible in two thirds of the patients. This offers the opportunity to improve specific diagnostics and therapy for patients with acute dizziness and vertigo even in primary care hospitals. Improved training for spoke hospital staff is needed to further increase the feasibility of vHIT.
Overt Oculomotor Behavior Reveals Covert Temporal Predictions
Authors: Tavano Alessandro , Kotz Sonja A.
Published: February 2022

Our eyes move in response to stimulus statistics, reacting to surprising events, and adapting to predictable ones. Cortical and subcortical pathways contribute to generating context-specific eye-movement dynamics, and oculomotor dysfunction is recognized as one the early clinical markers of Parkinson's disease (PD). We asked if covert computations of environmental statistics generating temporal expectations for a potential target are registered by eye movements, and if so, assuming that temporal expectations rely on motor system efficiency, whether they are impaired in PD. We used a repeating tone sequence, which generates a hazard rate distribution of target probability, and analyzed the distribution of blinks when participants were waiting for the target, but the target did not appear. Results show that, although PD participants tend to produce fewer and less temporally organized blink events relative to healthy controls, in both groups blinks became more suppressed with increasing target probability, leading to a hazard rate of oculomotor inhibition effects. The covert generation of temporal predictions may reflect a key feature of cognitive resilience in Parkinson's Disease.