bluuebunny/crossref_metadata_2025 huggingface dataset:
Pembrolizumab Induces an Unexpected Conformational Change in the CC′-loop of PD-1
Authors: Roither Bernhard , Oostenbrink Chris , Pfeiler Georg , Koelbl Heinz , Schreiner Wolfgang
Published: December 2020

To improve cancer immunotherapy, a clearer understanding of key targets such as the immune checkpoint receptor PD-1 is essential. The PD-1 inhibitors nivolumab and pembrolizumab were recently approved by the FDA. The CC′-loop of PD-1 has been identified as a hotspot for drug targeting. Here, we investigate the influence of nivolumab and pembrolizumab on the molecular motion of the CC′-loop of PD-1. We performed molecular dynamics simulations on the complete extracellular domain of PD-1, in complex with PD-L1, and the blocking antibodies nivolumab and pembrolizumab. Conformations of the CC′-loop were analyzed unsupervised with the Daura et al. clustering algorithm and multidimensional scaling. Surprisingly, two conformations found were seen to correspond to the ‘open’ and ‘closed’ conformation of CC′-loop in apo-PD-1, already known from literature. Unsupervised clustering also surprisingly reproduced the natural ligand, PD-L1, exclusively stabilizing the ‘closed’ conformation, as also known from literature. Nivolumab, like PD-L1, was found to shift the equilibrium towards the ‘closed’ conformation, in accordance with the conformational selection model. Pembrolizumab, on the other hand, induced a third conformation of the CC′-loop which has not been described to date: Relative to the conformation ‘open’ the, CC′-loop turned 180° to form a new conformation which we called ‘overturned’. We show that the combination of clustering and multidimensional scaling is a fast, easy, and powerful method in analyzing structural changes in proteins. Possible refined antibodies or new small molecular compounds could utilize the flexibility of the CC′-loop to improve immunotherapy.
Nanomedicine: A Useful Tool against Glioma Stem Cells
Authors: Bozzato Elia , Bastiancich Chiara , Préat Véronique
Published: December 2020

The standard of care therapy of glioblastoma (GBM) includes invasive surgical resection, followed by radiotherapy and concomitant chemotherapy. However, this therapy has limited success, and the prognosis for GBM patients is very poor. Although many factors may contribute to the failure of current treatments, one of the main causes of GBM recurrences are glioma stem cells (GSCs). This review focuses on nanomedicine strategies that have been developed to eliminate GSCs and the benefits that they have brought to the fight against cancer. The first section describes the characteristics of GSCs and the chemotherapeutic strategies that have been used to selectively kill them. The second section outlines the nano-based delivery systems that have been developed to act against GSCs by dividing them into nontargeted and targeted nanocarriers. We also highlight the advantages of nanomedicine compared to conventional chemotherapy and examine the different targeting strategies that have been employed. The results achieved thus far are encouraging for the pursuit of effective strategies for the eradication of GSCs.
Pathogenetic Role and Clinical Implications of Regulatory RNAs in Biliary Tract Cancer
Authors: Ofoeyeno Nduka , Ekpenyong Emmanuel , Braconi Chiara
Published: December 2020

Biliary tract cancer (BTC) is characterised by poor prognosis and low overall survival in patients. This is generally due to minimal understanding of its pathogenesis, late diagnosis and limited therapeutics in preventing or treating BTC patients. Non-coding RNA (ncRNA) are small RNAs (mRNA) that are not translated to proteins. ncRNAs were considered to be of no importance in the genome, but recent studies have shown they play essential roles in biology and oncology such as transcriptional repression and degradation, thus regulating mRNA transcriptomes. This has led to investigations into the role of ncRNAs in the pathogenesis of BTC, and their clinical implications. In this review, the mechanisms of action of ncRNA are discussed and the role of microRNAs in BTC is summarised. The scope of this review will be limited to miRNA as they have been shown to play the most significant roles in BTC progression. There is huge potential in miRNA-based biomarkers and therapeutics in BTC, but more studies, research and technological advancements are required before it can be translated into clinical practice for patients.
Metabolic Reprogramming by Malat1 Depletion in Prostate Cancer
Authors: Nanni Simona , Aiello Aurora , Salis Chiara , Re Agnese , Cencioni Chiara , Bacci Lorenza , Pierconti Francesco , Pinto Francesco , Ripoli Cristian , Ostano Paola , Baroni Silvia , Lazzarino Giacomo , Tavazzi Barbara , Pugliese Dario , Bassi PierFrancesco , Grassi Claudio , Panunzi Simona , Chiorino Giovanna , Pontecorvi Alfredo , Gaetano Carlo , Farsetti Antonella
Published: December 2020

The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes growth and progression in prostate cancer (PCa); however, little is known about its possible impact in PCa metabolism. The aim of this work has been the assessment of the metabolic reprogramming associated with MALAT1 silencing in human PCa cells and in an ex vivo model of organotypic slice cultures (OSCs). Cultured cells and OSCs derived from primary tumors were transfected with MALAT1 specific gapmers. Cell growth and survival, gene profiling, and evaluation of targeted metabolites and metabolic enzymes were assessed. Computational analysis was made considering expression changes occurring in metabolic markers following MALAT1 targeting in cultured OSCs. MALAT1 silencing reduced expression of some metabolic enzymes, including malic enzyme 3, pyruvate dehydrogenase kinases 1 and 3, and choline kinase A. Consequently, PCa metabolism switched toward a glycolytic phenotype characterized by increased lactate production paralleled by growth arrest and cell death. Conversely, the function of mitochondrial succinate dehydrogenase and the expression of oxidative phosphorylation enzymes were markedly reduced. A similar effect was observed in OSCs. Based on this, a predictive algorithm was developed aimed to predict tumor recurrence in a subset of patients. MALAT1 targeting by gapmer delivery restored normal metabolic energy pathway in PCa cells and OSCs.
Metabolite Profiling of Alangium salviifolium Bark Using Advanced LC/MS and GC/Q-TOFTechnology
Authors: Siddaiah Chandranayaka , Kumar BM Anil , Deepak Saligrama Adavigowda , Lateef Syed Salman , Nagpal Saurabh , Rangappa Kanchugarakoppal S. , Mohan Chakrabhavi D. , Rangappa Shobith , Kumar S Madan , Sharma Minaxi , Gupta Vijai Kumar
Published: December 2020

There is an urge for traditional herbal remedies as an alternative to modern medicine in treating several ailments. Alangium salviifolium is one such plant, used traditionally to treat several diseases. In several reports, there are findings related to the use of this plant extract that demonstrate its therapeutic value. However, very few attempts have been made to identify the extensive metabolite composition of this plant. Here, we performed metabolite profiling and identification from the bark of A. salviifolium by extracting the sample in organic and aqueous solvents. The organic and aqueous extracts were fraction-collected using the Agilent 1260 Analytical Scale Fraction Collection System. Each of the fractions was analyzed on Liquid Chromatogaphy/Quadrupole Time-of-Flight LC/Q-TOF and Gas Chromatography/Quadrupole Time-of-Flight GC/instruments. The Liquid Chromatography/Mass Spectrometry (LC/MS) analyses were performed using Hydrophilic Ineraction Liquid Chromatography (HILIC), as well as reversed-phase chromatography using three separate, orthogonal reverse phase columns. Samples were analyzed using an Agilent Jet Stream (AJS) source in both positive and negative ionization modes. The compounds found were flavonoids, fatty acids, sugars, and terpenes. Eighty-one secondary metabolites were identified as having therapeutic potential. The data produced was against the METLIN database using accurate mass and/or MS/MS library matching. Compounds from Alangium that could not be identified by database or library matching were subsequently searched against the ChemSpider) database of over 30 million structures using MSMS data and Agilent MSC software.In order to identify compounds generated by GC/MS, the data were searched against the AgilentFiehn GCMS Metabolomics Library as well as the Wiley/NIST libraries.
Ariadne’s Thread in the Developing Cerebral Cortex: Mechanisms Enabling the Guiding Role of the Radial Glia Basal Process during Neuron Migration
Authors: Meyerink Brandon L. , Tiwari Neeraj K. , Pilaz Louis-Jan
Published: December 2020

Radial neuron migration in the developing cerebral cortex is a complex journey, starting in the germinal zones and ending in the cortical plate. In mice, migratory distances can reach several hundreds of microns, or millimeters in humans. Along the migratory path, radially migrating neurons slither through cellularly dense and complex territories before they reach their final destination in the cortical plate. This task is facilitated by radial glia, the neural stem cells of the developing cortex. Indeed, radial glia have a unique bipolar morphology, enabling them to serve as guides for neuronal migration. The key guiding structure of radial glia is the basal process, which traverses the entire thickness of the developing cortex. Neurons recognize the basal process as their guide and maintain physical interactions with this structure until the end of migration. Thus, the radial glia basal process plays a key role during radial migration. In this review, we highlight the pathways enabling neuron-basal process interactions during migration, as well as the known mechanisms regulating the morphology of the radial glia basal process. Throughout, we describe how dysregulation of these interactions and of basal process morphology can have profound effects on cortical development, and therefore lead to neurodevelopmental diseases.
Depletion of Embryonic Macrophages Leads to a Reduction in Angiogenesis in the Ex Ovo Chick Chorioallantoic Membrane Assay
Authors: Tay Hanna , Du Cheyne Charis , Demeyere Kristel , De Craene Jurgen , De Bels Lobke , Meyer Evelyne , Zijlstra Andries , Spiegelaere Ward De
Published: December 2020

Macrophages play an important but poorly understood role in angiogenesis. To investigate their role in vessel formation, relevant in vivo models are crucial. Although the chick chorioallantoic membrane (CAM) model has been frequently used as an angiogenesis assay, limited data are available on the involvement of chicken macrophages in this process. Here, we describe a method to deplete macrophages in the ex ovo chick CAM assay by injection of clodronate liposomes and show that this depletion directly affects vascularisation of collagen onplants. Chicken embryos were injected intravenously with either clodronate or phosphate-buffered saline (PBS) liposomes, followed by placement of collagen type I plugs on the CAM to quantify angiogenic ingrowth. Clodronate liposome injection led to a significant 3.4-fold reduction of macrophages compared with control embryos as measured by immunohistochemistry and flow cytometry. Furthermore, analysis of vessel ingrowth into the collagen plugs revealed a significantly lower angiogenic response in macrophage-depleted embryos compared with control embryos, indicating that chicken embryonic macrophages play an essential function in the development of blood vessels. These results demonstrate that the chick CAM assay provides a promising model to investigate the role of macrophages in angiogenesis.
IL-6 Is Not Absolutely Essential for the Development of a TH17 Immune Response after an Aerosol Infection with Mycobacterium tuberculosis H37rv
Authors: Ritter Kristina , Sodenkamp Jan Christian , Hölscher Alexandra , Behrends Jochen , Hölscher Christoph
Published: December 2020

Anti-inflammatory treatment of chronic inflammatory diseases often increases susceptibility to infectious diseases such as tuberculosis (TB). Since numerous chronic inflammatory and autoimmune diseases are mediated by interleukin (IL)-6-induced T helper (TH) 17 cells, a TH17-directed anti-inflammatory therapy may be preferable to an IL-12-dependent TH1 inhibition in order to avoid reactivation of latent infections. To assess, however, the risk of inhibition of IL-6-dependent TH17-mediated inflammation, we examined the TH17 immune response and the course of experimental TB in IL-6- and T-cell-specific gp130-deficient mice. Our study revealed that the absence of IL-6 or gp130 on T cells has only a minor effect on the development of antigen-specific TH1 and TH17 cells. Importantly, these gene-deficient mice were as capable as wild type mice to control mycobacterial infection. Together, in contrast to its key function for TH17 development in other inflammatory diseases, IL-6 plays an inferior role for the generation of TH17 immune responses during experimental TB.
Modification, Degradation and Evaluation of a Few Organic Coatings for Some Marine Applications
Authors: Song Guang-Ling , Feng Zhenliang
Published: December 2020

Organic coatings for marine applications must have great corrosion protection and antifouling performance. This review presents an overview of recent investigations into coating microstructure, corrosion protection performance, antifouling behavior, and evaluation methods, particularly the substrate effect and environmental influence on coating protectiveness, aiming to improve operational practice in the coating industry. The review indicates that the presence of defects in an organic coating is the root cause of the corrosion damage of the coating. The protection performance of a coating system can be enhanced by proper treatment of the substrate and physical modification of the coating. Environmental factors may synergistically accelerate the coating degradation. The long-term protection performance of a coating system is extremely difficult to predict without coating defect information. Non-fouling coating and self-repairing coatings may be promising antifouling approaches. Based on the review, some important research topics are suggested, such as the exploration of rapid evaluation methods, the development of long-term cost-effective antifouling coatings in real marine environments.
Biomechanical Interfaces of Corticotomies on Periodontal Tissue Remodeling during Orthodontic Tooth Movement
Authors: Liu Ruojing , Huang Li , Xiao Xiaoyue , Guan Yuzhe , Jiang Yukun , Yin Xing , Zou Shujuan , Ye Qingsong
Published: December 2020

Corticotomy is an effective approach in accelerating orthodontic tooth movement (OTM) in clinical treatment. Corticotomy causes regional acceleratory phenomenon (RAP) in the alveolar bone of surgical sites. However, the molecular mechanism of RAP after corticotomy remains unclear. Herein, we established a mouse model to study the biomechanical interfaces of corticotomy-assisted OTM and to investigate the histological responses and underlying cellular mechanism. A total of 144 male C57BL/6 mice were randomly assigned into four groups: corticotomy alone (Corti), sham operation (Sham), corticotomy with tooth movement (Corti + TM), and sham operation with tooth movement (Sham + TM). Nickel–titanium orthodontic springs were applied to trigger tooth movement. Mice were sacrificed on Post-Surgery Day (PSD) 3, 7, 14, 21, and 28 for radiographic, histological, immunohistochemical, and molecular biological analyses. The results reveal that corticotomy significantly promoted alveolar bone turnover and periodontal tissue remodeling. During orthodontic tooth movement, corticotomy significantly promoted osteogenic and proliferative activity, accelerated tooth movement, and eliminated root resorption by upregulating Wnt signal pathway.
Performance Optimization of MANET Networks through Routing Protocol Analysis
Authors: Priyambodo Tri Kuntoro , Wijayanto Danur , Gitakarma Made Santo
Published: December 2020

A Mobile Ad Hoc Network (MANET) protocol requires proper settings to perform data transmission optimally. To overcome this problem, it is necessary to select the correct routing protocol and use the routing protocol’s default parameter values. This study examined the effect of route request parameters, such as RREQ_RETRIES and MAX_RREQ_TIMOUT, on the Ad Hoc On-demand Distance Vector (AODV) protocol, which was then compared with the default AODV performance Optimized Link State Routing (OLSR) protocols. The performance metrics used for measuring performance were Packet Delivery Ratio (PDR), throughput, delay, packet loss, energy consumption, and routing overhead. The results show that the OLSR protocol has a smaller delay than the AODV protocol, while in other measurements, the AODV protocol is better than OLSR. By reducing the combination value of RREQ_RETRIES, MAX_RREQ_TIMEOUT in AODV routing to (2, 10 s) and (3, 5 s), the protocol’s performance can be improved. The two combinations result in an average increase in throughput performance of 3.09%, a decrease in delay of 17.7%, a decrease in packet loss of 27.15%, and an increase in PDR of 4.8%. For variations in the speed of movement of nodes, 20 m/s has the best performance, while 5 m/s has the worst performance.
Micro-Plasma Assisted Synthesis of ZnO Nanosheets for the Efficient Removal of Cr6+ from the Aqueous Solution
Authors: Kumar Pawan , Saini Meenu , Singh Maninder , Chhillar Nidhi , S. Dehiya Brijnandan , Kishor Kamal , Alharthi Fahad A. , Al-Zaqri Nabil , Ali Alghamdi Abdulaziz
Published: December 2020

Herein, we report a micro-plasma assisted solvothermal synthesis and characterization of zinc oxide nanosheets (ZnO-NSs) and their application for the removal of Cr6+ ion from aqueous solution. The morphological investigations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the high-density growth of nanosheets with the typical sizes in the range of 145.8–320.25 nm. The typical surface area of the synthesized ZnO-NSs, observed by Brunauer-Emmett-Teller (BET), was found to be 948 m2/g. The synthesized ZnO-NSs were used as efficient absorbent for the removal of Cr6+ ion from aqueous solution. Various parameters such as pH, contact time, amount of adsorbate and adsorbent on the removal efficiency of Cr6+ ion was optimized and presented in this paper. At optimized conditions, the highest value for removal was 87.1% at pH = 2 while the calculated maximum adsorption capacity was ~87.37 mg/g. The adsorption isotherm data were found to be best fitted to Temkin adsorption isotherm and the adsorption process followed the pseudo-first-order kinetics. Furthermore, the toxicity of ZnO-NSs were also examined against fibroblast cells, which show favorable results and proved that it can be used for wastewater treatment.
A Review on Graphene’s Light Stabilizing Effects for Reduced Photodegradation of Polymers
Authors: Karimi Samira , Helal Emna , Gutierrez Giovanna , Moghimian Nima , Madinehei Milad , David Eric , Samara Mazen , Demarquette Nicole
Published: December 2020

Graphene, the newest member of the carbon’s family, has proven its efficiency in improving polymers’ resistance against photodegradation, even at low loadings equal to 1 wt% or lower. This protective role involves a multitude of complementary mechanisms associated with graphene’s unique geometry and chemistry. In this review, these mechanisms, taking place during both the initiation and propagation steps of photodegradation, are discussed concerning graphene and graphene derivatives, i.e., graphene oxide (GO) and reduced graphene oxide (rGO). In particular, graphene displays important UV absorption, free radical scavenging, and quenching capabilities thanks to the abundant π-bonds and sp2 carbon sites in its hexagonal lattice structure. The free radical scavenging effect is also partially linked with functional hydroxyl groups on the surface. However, the sp2 sites remain the predominant player, which makes graphene’s antioxidant effect potentially stronger than rGO and GO. Besides, UV screening and oxygen barriers are active protective mechanisms attributed to graphene’s high surface area and 2D geometry. Moreover, the way that graphene, as a nucleating agent, can improve the photostability of polymers, have been explored as well. These include the potential effect of graphene on increasing polymer’s glass transition temperature and crystallinity.
Plant-Pollinator Networks in Savannas of Burkina Faso, West Africa
Authors: Stein Katharina , Coulibaly Drissa , Balima Larba Hubert , Goetze Dethardt , Linsenmair Karl Eduard , Porembski Stefan , Stenchly Kathrin , Theodorou Panagiotis
Published: December 2020

West African savannas are severely threatened with intensified land use and increasing degradation. Bees are important for terrestrial biodiversity as they provide native plant species with pollination services. However, little information is available regarding their mutualistic interactions with woody plant species. In the first network study from sub-Saharan West Africa, we investigated the effects of land-use intensity and climatic seasonality on plant–bee communities and their interaction networks. In total, we recorded 5686 interactions between 53 flowering woody plant species and 100 bee species. Bee-species richness and the number of interactions were higher in the low compared to medium and high land-use intensity sites. Bee- and plant-species richness and the number of interactions were higher in the dry compared to the rainy season. Plant–bee visitation networks were not strongly affected by land-use intensity; however, climatic seasonality had a strong effect on network architecture. Null-model corrected connectance and nestedness were higher in the dry compared to the rainy season. In addition, network specialization and null-model corrected modularity were lower in the dry compared to the rainy season. Our results suggest that in our study region, seasonal effects on mutualistic network architecture are more pronounced compared to land-use change effects. Nonetheless, the decrease in bee-species richness and the number of plant–bee interactions with an increase in land-use intensity highlights the importance of savanna conservation for maintaining bee diversity and the concomitant provision of ecosystem services.
Meiofauna in a Potential Deep-Sea Mining Area—Influence of Temporal and Spatial Variability on Small-Scale Abundance Models
Authors: Uhlenkott Katja , Vink Annemiek , Kuhn Thomas , Gillard Benjamin , Martínez Arbizu Pedro
Published: December 2020

In large areas of the Clarion Clipperton Fracture Zone (northeast Pacific), exploration of deep-sea polymetallic nodules as a potential source of high-technology metals is ongoing. Deep-sea mining may have a severe impact on the benthic communities. Here, we investigated meiofauna communities in the abyss at the scale of a prospective mining operation area. Random forest regressions were computed to spatially predict continuous layers of environmental variables as well as the distribution of meiofauna abundance across the area. Significant models could be computed for 26 sediment and polymetallic nodule parameters. Meiofauna abundance, taxon richness and diversity were also modelled, as well as abundance of the taxon Nematoda. Spatial correlation is high if the predictions of meiofauna are either based on bathymetry and backscatter or include sediment and nodule variables; Pearson’s correlation coefficient varies between 0.42 and 0.91. Comparison of differences in meiofauna abundance between different years shows that spatial patterns do change, with an elevated abundance of meiofauna in the eastern part of the study area in 2013. On the spatial scale of a potential mining operation, distribution models prove to be a useful tool to gain insight into both temporal variability and the influence of potential environmental drivers on meiofauna distribution.
Co-Occurrence of Hotspot Point Mutation and Novel Deletion Mutation of TERT Promoter in Solid Variant Papillary Thyroid Carcinoma in a Patient with Synchronous Esophageal Cancer
Authors: Han Jiheun , Oh Young Lyun , Kim Jung-Sun
Published: December 2020

(1) Introduction: Telomerase reverse transcriptase (TERT) promoter mutations are associated with unfavorable clinical outcomes in papillary thyroid carcinomas (PTCs). Two substitution mutations, C228T (c.1-124C>T) and C250T (c.1-146C>T), make up most of the mutations and occur in a mutually exclusive manner. (2) Case presentation: A 72-year-old man was initially referred to a tertiary hospital for treatment of esophageal cancer. Preoperative imaging revealed a 3.2 cm thyroid nodule pathologically diagnosed as PTC on needle biopsy. The patient underwent thyroid lobectomy with esophagectomy and was finally diagnosed with synchronous solid variant PTC (SVPTC) and esophageal squamous cell carcinoma. Sanger sequencing using DNA from the thyroid tumor showed an indel mutation, c.1-132_1-124delinsT, composed of a deletion (c.1-132_1-125del) as well as a hotspot mutation (c.1-124C>T(C228T)) in the TERT promoter. (3) Conclusions: This is the first report of PTC harboring a novel deletion along with a hotspot mutation in the TERT promoter in a patient with synchronous esophageal squamous cell carcinoma.
On the Variability of Functional Connectivity and Network Measures in Source-Reconstructed EEG Time-Series
Authors: Fraschini Matteo , La Cava Simone Maurizio , Didaci Luca , Barberini Luigi
Published: December 2020

The idea of estimating the statistical interdependence among (interacting) brain regions has motivated numerous researchers to investigate how the resulting connectivity patterns and networks may organize themselves under any conceivable scenario. Even though this idea has developed beyond its initial stages, its practical application is still far away from being widespread. One concurrent cause may be related to the proliferation of different approaches that aim to catch the underlying statistical interdependence among the (interacting) units. This issue has probably contributed to hindering comparisons among different studies. Not only do all these approaches go under the same name (functional connectivity), but they have often been tested and validated using different methods, therefore, making it difficult to understand to what extent they are similar or not. In this study, we aim to compare a set of different approaches commonly used to estimate the functional connectivity on a public EEG dataset representing a possible realistic scenario. As expected, our results show that source-level EEG connectivity estimates and the derived network measures, even though pointing to the same direction, may display substantial dependency on the (often arbitrary) choice of the selected connectivity metric and thresholding approach. In our opinion, the observed variability reflects the ambiguity and concern that should always be discussed when reporting findings based on any connectivity metric.
Long Short-Term Memory Network-Based Normal Pattern Group for Fault Detection of Three-Shaft Marine Gas Turbine
Authors: Bai Mingliang , Liu Jinfu , Ma Yujia , Zhao Xinyu , Long Zhenhua , Yu Daren
Published: December 2020

Fault detection and diagnosis can improve safety and reliability of gas turbines. Current studies on gas turbine fault detection and diagnosis mainly focus on the case of abundant fault samples. However, fault data are rare or even unavailable for gas turbines, especially newly-run gas turbines. Aiming to realize fault detection with only normal data, this paper proposes the concept of normal pattern group. A group of long-short term memory (LSTM) networks are first used for characterizing the mapping relationships among measurable parameters of healthy three-shaft gas turbines. Experiments show that the proposed method can detect all 13 common gas path faults of three-shaft gas turbines sensitively while remaining low false alarm rate. Comparison experiment with single normal pattern model verifies the necessaries and superiorities of using normal pattern group. Meanwhile, comparison between LSTM network and other methods including support vector regression, single-layer feedforward neural network, extreme learning machine and Elman recurrent neural network verifies the superiorities of LSTM network in fault detection. Furthermore, comparison experiment with four common one-class classifiers further verifies the superiorities of the proposed method. This also indicates the superiorities of data-driven methods and gas turbine principle fusion to some extent.
Biogeographic Changes in Forest Soil Microbial Communities of Offshore Islands—A Case Study of Remote Islands in Taiwan
Authors: Chang Ed-Haun , Tsai Isheng Jason , Jien Shih-Hao , Tian Guanglong , Chiu Chih-Yu
Published: December 2020

Biogeographic separation has been an important cause of faunal and floral distribution; however, little is known about the differences in soil microbial communities across islands. In this study, we determined the structure of soil microbial communities by analyzing phospholipid fatty acid (PLFA) profiles and comparing enzymatic activities as well as soil physio-chemical properties across five subtropical granite-derived and two tropical volcanic (andesite-derived) islands in Taiwan. Among these islands, soil organic matter, pH, urease, and PLFA biomass were higher in the tropical andesite-derived than subtropical granite-derived islands. Principal component analysis of PLFAs separated these islands into three groups. The activities of soil enzymes such as phosphatase, β-glucosidase, and β-glucosaminidase were positively correlated with soil organic matter and total nitrogen. Redundancy analysis of microbial communities and environmental factors showed that soil parent materials and the climatic difference are critical factors affecting soil organic matter and pH, and consequently the microbial community structure.
Lentil Fortified Spaghetti: Technological Properties and Nutritional Characterization
Authors: Di Stefano Vita , Pagliaro Antonella , Del Nobile Matteo Alessandro , Conte Amalia , Melilli Maria Grazia
Published: December 2020

Lentil (Lens culinaris), consumed as a part of the diet worldwide, is a functional dietary ingredient that plays a function in human nutrition as a rich source of bioactive nutrients (low quantities of fat, sodium, and vitamin K; high content of potassium, essential amino acids, insoluble dietary fiber, and polyphenols). In this study spaghetti fortified with lentil flours (40% w/w) were developed and characterized. The addition of two different lentil flours significantly affected the sensory attributes and cooking properties of dry spaghetti. Therefore, the addition of carboxymethyl cellulose was adopted as technological option to improve the quality of fortified pasta; specifically, sensory acceptability, cooking loss, swelling index, and water absorption were studied. Chemical results highlighted that the addition of lentil to semolina significantly increased the content of lysine and threonine. It was observed an increase in essential and branched-chain amino acids. Contrary to what was expected, no increase in mono and polyunsaturated fatty acids was observed in fortified spaghetti, due to their loss during cooking, even after the addition of carboxymethyl cellulose.
In Vivo Digestion of Egg Products Enriched with DHA: Effect of the Food Matrix on DHA Bioavailability
Authors: Pineda-Vadillo Carlos , Nau Françoise , Guérin-Dubiard Catherine , Bourlieu Claire , Capozzi Francesco , Bordoni Alessandra , Dupont Didier
Published: December 2020

The aim of the present study was to determine to what extent the food matrix could affect the release of docosahexaenoic acid (DHA) during digestion and its incorporation into systemic circulation. In this aim, three DHA-enriched egg products having the same composition but different structure were developed: omelet, hard-boiled egg, and mousse. Then, nine pigs fitted with T-shape cannulas at duodenal level and a jugular venous catheter were fed with the DHA-enriched egg products, and duodenal effluents and plasma were collected throughout the postprandial period. Results highlighted an undeniable effect of the food matrix on digestion parameters and DHA bioavailability. The transit of DHA and protein through the duodenum was faster after the ingestion of the mousse than after the ingestion of the omelet and hard-boiled egg. While most of the DHA and protein ingested under the form of mousse had already passed through the duodenum 4.5 h after its ingestion, significantly higher quantities were still present in the case of the omelet and hard-boiled egg. In terms of bioavailability, the omelet was the most efficient vector for delivering DHA into systemic circulation. It supplied 56% and 120% more DHA than the hard-boiled egg and the mousse, respectively.
pcPromoter-CNN: A CNN-Based Prediction and Classification of Promoters
Authors: Shujaat Muhammad , Wahab Abdul , Tayara Hilal , Chong Kil To
Published: December 2020

A promoter is a small region within the DNA structure that has an important role in initiating transcription of a specific gene in the genome. Different types of promoters are recognized by their different functions. Due to the importance of promoter functions, computational tools for the prediction and classification of a promoter are highly desired. Promoters resemble each other; therefore, their precise classification is an important challenge. In this study, we propose a convolutional neural network (CNN)-based tool, the pcPromoter-CNN, for application in the prediction of promotors and their classification into subclasses σ70, σ54, σ38, σ32, σ28 and σ24. This CNN-based tool uses a one-hot encoding scheme for promoter classification. The tools architecture was trained and tested on a benchmark dataset. To evaluate its classification performance, we used four evaluation metrics. The model exhibited notable improvement over that of existing state-of-the-art tools.
Whole Exome Sequencing Identifies Novel De Novo Variants Interacting with Six Gene Networks in Autism Spectrum Disorder
Authors: Kim Namshin , Kim Kyoung Hyoun , Lim Won-Jun , Kim Jiwoong , Kim Soon Ae , Yoo Hee Jeong
Published: December 2020

Autism spectrum disorder (ASD) is a highly heritable condition caused by a combination of environmental and genetic factors such as de novo and inherited variants, as well as rare or common variants among hundreds of related genes. Previous genome-wide association studies have identified susceptibility genes; however, most ASD-associated genes remain undiscovered. This study aimed to examine rare de novo variants to identify genetic risk factors of ASD using whole exome sequencing (WES), functional characterization, and genetic network analyses of identified variants using Korean familial dataset. We recruited children with ASD and their biological parents. The clinical best estimate diagnosis of ASD was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5TM), using comprehensive diagnostic instruments. The final analyses included a total of 151 individuals from 51 families. Variants were identified and filtered using the GATK Best Practices for bioinformatics analysis, followed by genome alignments and annotation to the reference genome assembly GRCh37 (liftover to GRCh38), and further annotated using dbSNP 154 build databases. To evaluate allele frequencies of de novo variants, we used the dbSNP, gnomAD exome v2.1.1, and genome v3.0. We used Ingenuity Pathway Analysis (IPA, Qiagen) software to construct networks using all identified de novo variants with known autism-related genes to find probable relationships. We identified 36 de novo variants with potential relations to ASD; 27 missense, two silent, one nonsense, one splice region, one splice site, one 5′ UTR, and one intronic SNV and two frameshift deletions. We identified six networks with functional relationships. Among the interactions between de novo variants, the IPA assay found that the NF-κB signaling pathway and its interacting genes were commonly observed at two networks. The relatively small cohort size may affect the results of novel ASD genes with de novo variants described in our findings. We did not conduct functional experiments in this study. Because of the diversity and heterogeneity of ASD, the primary purpose of this study was to investigate probable causative relationships between novel de novo variants and known autism genes. Additionally, we based functional relationships with known genes on network analysis rather than on statistical analysis. We identified new variants that may underlie genetic factors contributing to ASD in Korean families using WES and genetic network analyses. We observed novel de novo variants that might be functionally linked to ASD, of which the variants interact with six genetic networks.
APOE Variants in an Iberian Alzheimer Cohort Detected through an Optimized Sanger Sequencing Protocol
Authors: González Ricardo D. , Gomes Iva , Gomes Catarina , Rocha Rita , Durães Luís , Sousa Patrícia , Figueruelo Manuel , Rodríguez Maria , Pita Carmen , Hornero Roberto , Gómez Carlos , Lopes Alexandra M. , Pinto Nádia , Martins Sandra
Published: December 2020

The primary genetic risk factor for late onset Alzheimer’s disease (LOAD) is the APOE4 allele of Apolipoprotein E (APOE) gene. The three most common variants of APOE are determined by single nucleotide polymorphisms (SNPs) rs429358 and rs7412. Our aim was to estimate allele and genotype frequencies of APOE variants in an Iberian cohort, thus helping to understand differences in APOE-related LOAD risk observed across populations. We analyzed saliva or buccal swab samples from 229 LOAD patients and 89 healthy elderly controls (≥68 years old) from Northern Portugal and Castile and León region, Spain. The genotyping was performed by Sanger sequencing, optimized to overcome GC content drawbacks. Results obtained in our Iberian LOAD and control cohorts are in line with previous large meta-analyses on APOE frequencies in Caucasian populations; however, we found differences in allele frequencies between our Portuguese and Spanish subgroups of AD patients. Moreover, when comparing studies from Iberian and other Caucasian cohorts, differences in APOE2 and APOE4 frequencies and subsequent different APOE-related LOAD risks must be clarified. These results show the importance of studying genetic variation at the APOE gene in different populations (including analyses at a regional level) to increase our knowledge about its clinical significance.
Features That Favor the Prediction of the Emplacement Location of Maar Volcanoes: A Case Study in the Central Andes, Northern Chile
Authors: Ureta Gabriel , Németh Károly , Aguilera Felipe , González Rodrigo
Published: December 2020

Maar volcanoes are monogenetic landforms whose craters cut below the pre-eruptive surface and are surrounded by a tephra ring. Both the maar crater and the surrounding tephra rim deposits are typically formed due to magma–water explosive interactions. Northern Chile is located in the Central Volcanic Zone of the Andes where, in literature, 14 maars have been recognized as parasite (6) and individual (8) volcanoes. Amongst these individual maars, 3 of them, namely the Tilocálar Sur, Cerro Tujle, and Cerro Overo volcanoes, are not related to calderas and were emplaced <1 Ma ago by magmatic explosive-effusive and phreatomagmatic eruptions. Based on the evolution and control of the volcanic eruptive styles of these three maars, which have been determined in previous research through fieldwork, stratigraphic, morphometric, textural (density and vesicularity), petrographic, and geochemical analyses, a set of key features that favor a prediction of the emplacement location of maar volcanoes in Central Andes, northern Chile are proposed. The set of features that permit and favor the growth mechanisms for maar formations corresponds to (i) a compressive tectonic setting (e.g., ridge structures), (ii) groundwater recharge (e.g., snowmelt and seasonal rainfall), (iii) the lithological setting (e.g., layers of low permeability), (iv) the presence of aquifer and/or endorheic basins (e.g., lakes or salars), and (v) a period of stress relaxation that permits magma ascent to the surface in volcanically active areas. Considering these characteristics, it is possible to identify places where phreatomagmatic eruption can occur. If the magma ascent flux is lower than the groundwater flux, this can lead to a phreatomagmatic eruption because of groundwater coming into contact with the magma. These eruptive features evidence internal—and external—factors that play an essential role in the transition from explosive-effusive magmatic to phreatomagmatic volcanic eruption styles during the same eruptive period that is one of the biggest challenges in volcanic hazard evaluations. Although, in this contribution, a set of features that permit and favor the growth mechanisms for a prediction of the emplacement location of maars in northern Chile is proposed, these considerations could also be applied to identify potential locations in other parts of the world where magma–water interaction eruption could occur. Therefore, this approach could be useful in the prediction of hydromagmatic volcanic eruptions and, thus, in mitigating the impact of volcanic hazard for the inhabitants of the surrounding areas.
Differences in and Prognostic Value of Quality of Life Data in Rectal Cancer Patients with and without Distant Metastases
Authors: Frank Fabian , Hecht Markus , Loy Florian , Rutzner Sandra , Fietkau Rainer , Distel Luitpold
Published: December 2020

(1) Background: Individualization of treatment is a major challenge in oncology and requires a variety of predictive and prognostic parameters. In addition to tumor biology analyses, baseline health-related quality of life might be a valid tool to predict overall survival. This study was conducted to evaluate the prognostic relevance of baseline quality of life data in patients with rectal cancer. In this context, differences between patients with and without distant metastases were of particular interest. (2) Methods: Our cohort included 258 patients with rectal cancer treated in the radiotherapy department of the University Hospital Erlangen. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ C30) and colorectal cancer questionnaire (CR38). Clinical and survival data were provided by the Gießener Tumor Documentation System (GTDS) of the Comprehensive Cancer Center Erlangen-EMN (CCC, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany). Statistical analyses were performed using Kaplan–Meier analyses and univariate and multivariate Cox regression. (3) Results: A cohort of 258 patients with rectal adenocarcinoma was analyzed including 50 patients (19.4%) with metastatic disease. No differences were observed between patients with and without distant metastases in most areas of quality of life studied, with the exception of physical function, loss of appetite, chemotherapy side effects and weight loss. Gender, baseline physical function, sexual function, diarrhea, and weight loss over time had a prognostic value in the entire cohort. Appetite loss was an additional prognostic parameter in patients with distant metastases. (4) Conclusions: The quality of life of patients with metastatic disease differed only slightly from non-metastatic patients. Health-related quality of life data provide prognostic information for patients with rectal cancer.
Genome-Wide Characterization of Cucumber (Cucumis sativus L.) GRAS Genes and Their Response to Various Abiotic Stresses
Authors: Li Caixia , Dong Shaoyun , Liu Xiaoping , Bo Kailiang , Miao Han , Beckles Diane M. , Zhang Shengping , Gu Xingfang
Published: December 2020

The GRAS (gibberellic acid insensitive, repressor of GAI, and scarecrow) proteins are a family of plant-specific transcription factors that regulate plant growth, development, and stress response. Currently, the role of GRAS transcription factors in various abiotic stress responses has not been systematically studied in cucumber (Cucumis sativus L.), a popular vegetable crop. Here, we provide a comprehensive bioinformatics analysis of the 35 GRAS genes identified in the cucumber genome. In this study, cucumber genotypes, i.e., “CG104”, which is stress-tolerant, and genotype “CG37”, which is stress-sensitive, were examined to provide insight on potential differences in the GRAS-regulated abiotic stress pathways. Transcriptional analysis by RNA-seq or qRT-PCR of these two genotypes revealed common and divergent functions of CsGRAS genes regulated by low and high temperatures, salinity, and by exposure to the phytohormones gibberellin (GA) and abscisic acid (ABA). Notably, CsGRAS2 (DELLA) and CsGRAS26 (LISCL) were regulated by all abiotic stresses and hormone treatments, suggesting that they may function in the biological cross-talk between multiple signaling pathways. This study provides candidate genes for improving cucumber tolerance to various environmental stresses.
Welcome to Hydrogen—A New International and Interdisciplinary Open Access Journal of Growing Interest in Our Society
Authors: Marnellos George E. , Klassen Thomas
Published: December 2020

The 2018 Intergovernmental Panel on Climate Change (IPCC) report [...]
Effects of Lactoferrin on Prevention of Acute Gastrointestinal Symptoms in Winter: A Randomized, Double-Blinded, Placebo-Controlled Trial for Staff of Kindergartens and Nursery Schools in Japan
Authors: Mizuki Masaru , Tsukahara Teruomi , Oda Hirotsugu , Tanaka Miyuki , Yamauchi Koji , Abe Fumiaki , Nomiyama Tetsuo
Published: December 2020

This study investigated the preventive effects of lactoferrin (LF) on subjective acute gastrointestinal symptoms during the winter in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The eligible subjects were healthy adults working at kindergartens and nursery schools. We randomized the subjects to the Placebo group (0 mg/day), the Low LF group (200 mg/day), and the High LF group (600 mg/day) for 12 weeks. The prevalence of acute gastrointestinal symptoms was significantly lower in the High LF (13/112 vs. 26/116; p = 0.030) and the Low LF (13/107 vs. 26/116; p = 0.040) groups than in the Placebo group. The adjusted odds ratio for the prevalence of acute gastrointestinal symptoms was 2.78 (95% CI: 1.19–6.47) in the Placebo group compared with the High LF group. LF is useful to prevent acute gastrointestinal symptoms among childcare workers, who mainly consist of women.