bluuebunny/crossref_metadata_2025 huggingface dataset:
Branch Occlusion and Discoloration under the Natural Pruning of Mytilaria laosensis
Authors: Qin Guoming , Hao Jian , Yang Jinchang , Li Rongsheng , Yin Guangtian
Published: October 2019

The production of knot-free and high-quality wood can be a vital issue in silviculture and forest management. In this study, knot properties, branch occlusion, and wood discoloration were investigated in an 11-year-old Mytilaria laosensis plantation in Guangxi, China, to examine the effectiveness of natural pruning in reducing knot-related defects. A total of 1513 occluded branches from 20 trees were sampled and dissected. Occluded branches were most common at heights of 2–6 m, and the mean diameter of the occluded branches gradually increased with height from the base to 6 m. Linear and generalized linear mixed-effect models were developed to reveal the relationship between branch occlusion and discoloration. The mortality of branches was highest in the third and fourth year and it took roughly three to six years to occlude. The mixed-models indicated that the branch occlusion time was positively correlated with the occluded branch diameter and dead branch stub length, and negatively correlated with the stem radial increment during branch occlusion. Branch discoloration was positively correlated with the occluded branch diameter and branch occlusion time, and was negatively correlated with the branch angle. The probability of wood discoloration also increased with the branch occlusion time. Our findings contribute to a better understanding of the spatiotemporal allocation and internal characteristics of occluded branches, and provide a reference for growing high-quality M. laosensis wood.
How Socio-Economic Differences between Farmers Affect Forest Degradation in Western Mexico
Authors: Borrego Armonia , Skutsch Margaret
Published: October 2019

Many forests under community use in tropical countries become degraded and lose carbon stocks as a result of agricultural activities such as shifting cultivation and cattle grazing, although these processes rarely result in deforestation. A better understanding of processes specifically causing forest degradation may be of interest to policy makers concerned with the design of programs to conserve forests, for example under international policy on Reducing Emissions from Deforestation and Forest Degradation (REDD+). On the basis of data from a farmer survey carried out in the western Pacific area of Mexico, this study uses a cross-sectional regression model to identify the variables that explain variations between groups of farmers in the amounts of land temporarily cleared for shifting cultivation, which results in decreasing the density of forest biomass. We found that, contrary to common perception about shifting cultivation, within each community, many farmers, both richer and poorer, carry out shifting cultivation. Moreover, it is the wealthier farmers that are making more temporary clearances for such activities when compared with those with less resources. We conclude that, for effectiveness in the design of national programs for REDD+, intra-community differences in farmer status should be taken into account. Moreover, REDD+ interventions should consider the impacts of this program on farmers without rights to land.
Fiber Microsphere Coupled in a Taper for a Large Curvature Range
Authors: Robalinho Paulo , Frazão Orlando
Published: October 2019

This work consists of using an optical fiber microsphere as a sensor for a wide range of curvature radii. The microsphere was manufactured in a standard fiber with an electric arc. In order to maximize system efficiency, the microsphere was spliced in the center of a taper. This work revealed that the variations of the wavelength where the maxima and minima of the spectrum are located varies linearly with the curvature of the system with a maximum sensitive of 580 ± 20 (pm km). This is because the direction of the input beam in the microsphere depends on the system curvature, giving rise to interferometric variations within the microsphere.
Ion Mobility Spectrometry as a Potential Tool for Flavor Control in Chocolate Manufacture
Authors: Schmidt Carolin , Jaros Doris , Rohm Harald
Published: October 2019

Chocolate has a complex flavor profile composed of more than 600 volatile compounds that mainly arise from the thermo-mechanical treatment during roasting and conching. The aim of this study was to evaluate the applicability of ion mobility spectrometry (IMS), as a real-time method for process monitoring in chocolate manufacture. It is evident from the ion mobility (IM) fingerprint spectra that individual processing steps affect the signal intensities at particular drift time regions. The analysis of individual IM spectra by principal component analysis (PCA) revealed that it is possible to distinguish with respect to conching temperature and time. PCA also allowed identifying those parts of the IM spectra that were predominantly affected by the respective treatment. It was, on the basis of the IM flavor fingerprints and subsequent PCA, possible to distinguish between the different states of processing of bulk cocoa. The results of the study imply that, using appropriate post-data treatment, IMS could be used for process control in cocoa processing.
An Approach Based on the Protected Object for Dam-Break Flood Risk Management Exemplified at the Zipingpu Reservoir
Authors: Fan Congxiang , An Ruidong , Li Jia , Li Kefeng , Deng Yun , Li Yong
Published: October 2019

Dam-break flooding is a potential hazard for reservoirs that poses a considerable threat to human lives and property in downstream areas. Assessing the dam-break flood risk of the Zipingpu Reservoir in Chengdu, Sichuan Province, China, is critically important because this reservoir is located on the Longmen Shan fault, which experiences high seismic activity. In this paper, we develop an approach based on the protected object for dam-break flood risk management. First, we perform a numerical simulation of dam-break flooding in four possible dam break scenarios. Next, the flood areas are divided into 71 analysis units based on the administrative division. Based on the numerical simulation results and the socio-economic demographic data affected by a flood, the importance and risk level of each analysis unit is confirmed, and the flood risk map is established according to the classification results. Finally, multi-level flood risk management countermeasures are proposed according to the results of the unit classification shown in the map.
Automatic Detection of Objects in 3D Point Clouds Based on Exclusively Semantic Guided Processes
Authors: Ponciano Jean-Jacques , Trémeau Alain , Boochs Frank
Published: October 2019

In the domain of computer vision, object recognition aims at detecting and classifying objects in data sets. Model-driven approaches are typically constrained through their focus on either a specific type of data, a context (indoor, outdoor) or a set of objects. Machine learning-based approaches are more flexible but also constrained as they need annotated data sets to train the learning process. That leads to problems when this data is not available through the specialty of the application field, like archaeology, for example. In order to overcome such constraints, we present a fully semantic-guided approach. The role of semantics is to express all relevant knowledge of the representation of the objects inside the data sets and of the algorithms which address this representation. In addition, the approach contains a learning stage since it adapts the processing according to the diversity of the objects and data characteristics. The semantic is expressed via an ontological model and uses standard web technology like SPARQL queries, providing great flexibility. The ontological model describes the object, the data and the algorithms. It allows the selection and execution of algorithms adapted to the data and objects dynamically. Similarly, processing results are dynamically classified and allow for enriching the ontological model using SPARQL construct queries. The semantic formulated through SPARQL also acts as a bridge between the knowledge contained within the ontological model and the processing branch, which executes algorithms. It provides the capability to adapt the sequence of algorithms to an individual state of the processing chain and makes the solution robust and flexible. The comparison of this approach with others on the same use case shows the efficiency and improvement this approach brings.
Pharmacological Targeting of GLUT1 to Control Autoreactive T Cell Responses
Authors: Di Dedda Carla , Vignali Debora , Piemonti Lorenzo , Monti Paolo
Published: October 2019

An increasing body of evidence indicates that bio-energetic metabolism of T cells can be manipulated to control T cell responses. This potentially finds a field of application in the control of the T cell responses in autoimmune diseases, including in type 1 diabetes (T1D). Of the possible metabolic targets, Glut1 gained considerable interest because of its pivotal role in glucose uptake to fuel glycolysis in activated T cells, and the recent development of a novel class of small molecules that act as selective inhibitor of Glut1. We believe we can foresee a possible application of pharmacological Glut1 blockade approach to control autoreactive T cells that destroy insulin producing beta cells. However, Glut1 is expressed in a broad range of cells in the body and off-target and side effect are possible complications. Moreover, the duration of the treatment and the age of patients are critical aspects that need to be addressed to reduce toxicity. In this paper, we will review recent literature to determine whether it is possible to design a pharmacological Glut1 blocking strategy and how to apply this to autoimmunity in T1D.
FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions
Authors: Kim Misun , Kwon Yoojung , Jung Hyun Suk , Kim Youngmi , Jeoung Dooil
Published: October 2019

Anaphylaxis is an acute and life-threatening systemic reaction. Food, drug, aero-allergen and insect sting are known to induce anaphylaxis. Mast cells and basophils are known to mediate Immunoglobulin E (IgE)-dependent anaphylaxis, while macrophages, neutrophils and basophils mediate non IgE-dependent anaphylaxis. Histone deacetylases (HDACs) play various roles in biological processes by deacetylating histones and non-histones proteins. HDAC inhibitors can increase the acetylation of target proteins and affect various inflammatory diseases such as cancers and allergic diseases. HDAC3, a class I HDAC, is known to act as epigenetic and transcriptional regulators. It has been shown that HDAC3 can interact with the high-affinity Immunoglobulin E receptor (FcεRI), to mediate passive anaphylaxis and cellular interactions during passive anaphylaxis. Effects of HDAC3 on anaphylaxis, cellular interactions involving mast cells and macrophages during anaphylaxis, and any tumorigenic potential of cancer cells enhanced by mast cells will be discussed in this review. Roles of microRNAs that form negative feedback loops with hallmarks of anaphylaxis such as HDAC3 in anaphylaxis and cellular interactions will also be discussed. The roles of MCP1 regulated by HDAC3 in cellular interactions during anaphylaxis are discussed. Roles of exosomes in cellular interactions mediated by HDAC3 during anaphylaxis are also discussed. Thus, review might provide clues for development of drugs targeting passive anaphylaxis.
A Novel Paclitaxel Conjugate with Higher Efficiency and Lower Toxicity: A New Drug Candidate for Cancer Treatment
Authors: Falah Mizied , Rayan Mahmoud , Rayan Anwar
Published: October 2019

Paclitaxel-lipoate (IDD-1040) is a conjugate formed by the chemical joining of the two compounds, by condensing a lipoic acid moiety to the C2′ of paclitaxel. IDD-1040 was evaluated for its anti-tumor activity and potential druggability, using an in vivo non-small-cell, lung cancer (NSCLC) xenograft mouse model. In the in vivo studies, IDD-1040 showed a maximum tolerated dose (MTD) of 250 mg/kg compared to paclitaxel (PTX), with an MTD of 20 mg/kg. Most interesting, IDD-1040 demonstrated higher anti-tumor activity, and its inhibitory activity on tumor volume (cell growth) was dose-dependent. That anti-tumor activity persisted for two weeks after cessation of IDD-1040 treatment, as opposed to PTX cessation, after which the tumor relapsed, confirming that IDD-1040 exhibits superior tumor inhibition. Similar to PTX treatment, no marked body weight decrease was observed during IDD-1040 treatment, indicating a low toxicity profile. The increase in animal body weight noted over time was due to the increasing weight of tumors, recorded in all the mouse test groups. The results also showed that mortality rate of mice was reduced by treatment with IDD-1040, more so than with PTX. Furthermore, in a preliminary study on the ex vivo distribution of IDD-1040, neutropenia was primarily concentrated in the liver 1 h after injection, and most of the drug was metabolized by the liver in 24 h. All of these results demonstrate IDD-1040’s great potential as a candidate drug for cancer treatment.
Mitochondrial Calcium Uptake Is Instrumental to Alternative Macrophage Polarization and Phagocytic Activity
Authors: Tedesco Serena , Scattolini Valentina , Albiero Mattia , Bortolozzi Mario , Avogaro Angelo , Cignarella Andrea , Fadini Gian Paolo
Published: October 2019

Macrophages are highly plastic and dynamic cells that exert much of their function through phagocytosis. Phagocytosis depends on a coordinated, finely tuned, and compartmentalized regulation of calcium concentrations. We examined the role of mitochondrial calcium uptake and mitochondrial calcium uniporter (MCU) in macrophage polarization and function. In primary cultures of human monocyte-derived macrophages, calcium uptake in mitochondria was instrumental for alternative (M2) macrophage polarization. Mitochondrial calcium uniporter inhibition with KB-R7943 or MCU knockdown, which prevented mitochondrial calcium uptake, reduced M2 polarization, while not affecting classical (M1) polarization. Challenging macrophages with E. coli fragments induced spikes of mitochondrial calcium concentrations, which were prevented by MCU inhibition or silencing. In addition, mitochondria remodelled in M2 macrophages during phagocytosis, especially close to sites of E. coli internalization. Remarkably, inhibition or knockdown of MCU significantly reduced the phagocytic capacity of M2 macrophages. KB-R7943, which also inhibits the membrane sodium/calcium exchanger and Complex I, reduced mitochondria energization and cellular ATP levels, but such effects were not observed with MCU silencing. Therefore, phagocytosis inhibition by MCU knockdown depended on the impaired mitochondrial calcium buffering rather than changes in mitochondrial and cellular energy status. These data uncover a new role for MCU in alternative macrophage polarization and phagocytic activity.
Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators
Authors: Kajarabille Naroa , Latunde-Dada Gladys O.
Published: October 2019

Iron, the fourth most abundant element in the Earth’s crust, is vital in living organisms because of its diverse ligand-binding and electron-transfer properties. This ability of iron in the redox cycle as a ferrous ion enables it to react with H2O2, in the Fenton reaction, to produce a hydroxyl radical (•OH)—one of the reactive oxygen species (ROS) that cause deleterious oxidative damage to DNA, proteins, and membrane lipids. Ferroptosis is a non-apoptotic regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is triggered when the endogenous antioxidant status of the cell is compromised, leading to lipid ROS accumulation that is toxic and damaging to the membrane structure. Consequently, oxidative stress and the antioxidant levels of the cells are important modulators of lipid peroxidation that induce this novel form of cell death. Remedies capable of averting iron-dependent lipid peroxidation, therefore, are lipophilic antioxidants, including vitamin E, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1) and possibly potent bioactive polyphenols. Moreover, most of the enzymes and proteins that cascade or interact in the pathway of ferroptosis such as a subunit of the cystine/glutamate transporter xc− (SLC7A11), glutathione peroxidase 4 (GPX4), and the glutamate–cysteine ligase (GCLC) iron metabolism genes transferrin receptor 1 (TfR1) ferroportin, (Fpn) heme oxygenase 1 (HO-1) and ferritin are regulated by the antioxidant response element of the transcription factor, Nrf2. These, as well as other radical trapping antioxidants (RTAs), are discussed in the current review.
Silencing of Odorant-Binding Protein Gene OBP3 Using RNA Interference Reduced Virus Transmission of Tomato Chlorosis Virus
Authors: Shi Xiao-Bin , Wang Xue-Zhong , Zhang De-Yong , Zhang Zhan-Hong , Zhang Zhuo , Cheng Ju’E , Zheng Li-Min , Zhou Xu-Guo , Tan Xin-Qiu , Liu Yong
Published: October 2019

Tomato chlorosis virus (ToCV) is widespread, seriously impacting tomato production throughout the world. ToCV is semi-persistently transmitted by Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Currently, insect olfaction is being studied to develop novel pest control technologies to effectively control B. tabaci and whitefly-borne virus diseases. Despite current research efforts, no report has been published on the role of odorant-binding proteins (OBPs) in insect preference under the influence of plant virus. Our previous research showed that viruliferous B. tabaci preferred healthy plants at 48 h after virus acquisition. In this study, we determined the effect of OBPs on the host preference interactions of ToCV and whiteflies. Our results show that with the increase in acquisition time, the OBP gene expressions changed differently, and the OBP3 gene expression showed a trend of first rising and then falling, and reached the maximum at 48 h. These results indicate that OBP3 may participate in the host preference of viruliferous whiteflies to healthy plants. When the expression of the OBP3 gene was knocked down by an RNA interference (RNAi) technique, viruliferous Mediterranean (MED) showed no preference and the ToCV transmission rate was reduced by 83.3%. We conclude that OBP3 is involved in the detection of plant volatiles by viruliferous MED. Our results provide a theoretical basis and technical support for clarifying the transmission mechanism of ToCV by B. tabaci and could provide new avenues for controlling this plant virus and its vectors.
Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells
Authors: Vera Nelly , Acuña-Gallardo Stephanie , Grünenwald Felipe , Caceres-Verschae Albano , Realini Ornella , Acuña Rodrigo , Lladser Alvaro , Illanes Sebastián E. , Varas-Godoy Manuel
Published: October 2019

Despite the different strategies used to treat ovarian cancer, around 70% of women/patients eventually fail to respond to the therapy. Cancer stem cells (CSCs) play a role in the treatment failure due to their chemoresistant properties. This capacity to resist chemotherapy allows CSCs to interact with different components of the tumor microenvironment, such as mesenchymal stem cells (MSCs), and thus contribute to tumorigenic processes. Although the participation of MSCs in tumor progression is well understood, it remains unclear how CSCs induce the pro-tumorigenic activity of MSCs in response to chemotherapy. Small extracellular vesicles, including exosomes, represent one possible way to modulate any type of cell. Therefore, in this study, we evaluate if small extracellular vesicle (sEV) derived from ovarian cancer spheroids (OCS), which are enriched in CSCs, can modify the activity of MSCs to a pro-tumorigenic phenotype. We show that sEV released by OCS in response to cisplatin induce an increase in the migration pattern of bone marrow MSCs (BM-MSCs) and the secretion interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor A (VEGFA). Moreover, the factors secreted by BM-MSCs induce angiogenesis in endothelial cells and the migration of low-invasive ovarian cancer cells. These findings suggest that cisplatin could modulate the cargo of sEV released by CSCs, and these exosomes can further induce the pro-tumorigenic activity of MSCs.
Transforming Growth Factor-β3/Chitosan Sponge (TGF-β3/CS) Facilitates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells
Authors: Li Yangfan , Qiao Zhifen , Yu Fenglin , Hu Huiting , Huang Yadong , Xiang Qi , Zhang Qihao , Yang Yan , Zhao Yueping
Published: October 2019

Periodontal disease is the main reason for tooth loss in adults. Tissue engineering and regenerative medicine are advanced technologies used to manage soft and hard tissue defects caused by periodontal disease. We developed a transforming growth factor-β3/chitosan sponge (TGF-β3/CS) to repair periodontal soft and hard tissue defects. We investigated the proliferation and osteogenic differentiation behaviors of primary human periodontal ligament stem cells (hPDLSCs) to determine the bioactivity and potential application of TGF-β3 in periodontal disease. We employed calcein-AM/propidium iodide (PI) double labeling or cell membranes (CM)-Dil labeling coupled with fluorescence microscopy to trace the survival and function of cells after implantation in vitro and in vivo. The mineralization of osteogenically differentiated hPDLSCs was confirmed by measuring alkaline phosphatase (ALP) activity and calcium content. The levels of COL I, ALP, TGF-βRI, TGF-βRII, and Pp38/t-p38 were assessed by western blotting to explore the mechanism of bone repair prompted by TGF-β3. When hPDLSCs were implanted with various concentrations of TGF-β3/CS (62.5–500 ng/mL), ALP activity was the highest in the TGF-β3 (250 ng/mL) group after 7 d (p < 0.05 vs. control). The calcium content in each group was increased significantly after 21 and 28 d (p < 0.001 vs. control). The optimal result was achieved by the TGF-β3 (500 ng/mL) group. These results showed that TGF-β3/CS promotes osteogenic differentiation of hPDLSCs, which may involve the p38 mitogen-activated protein kinase (MAPK) signaling pathway. TGF-β3/CS has the potential for application in the repair of incomplete alveolar bone defects.
Effect of Zinc Supplementation on Renal Anemia in 5/6-Nephrectomized Rats and a Comparison with Treatment with Recombinant Human Erythropoietin
Authors: Feng Hui-Lin , Chen Yen-Hua , Jeng Sen-Shyong
Published: October 2019

Anemia is a severe complication in patients with chronic kidney disease (CKD). Treatment with exogenous erythropoietin (EPO) can correct anemia in many with CKD. We produced 5/6-nephrectomized rats that became uremic and anemic at 25 days post surgery. Injection of the anemic 5/6-nephrectomized rats with 2.8 mg zinc/kg body weight raised their red blood cell (RBC) levels from approximately 85% of the control to 95% in one day and continued for 4 days. We compared the effect of ZnSO4 and recombinant human erythropoietin (rHuEPO) injections on relieving anemia in 5/6-nephrectomized rats. After three consecutive injections, both the ZnSO4 and rHuEPO groups had significantly higher RBC levels (98 ± 6% and 102 ± 6% of the control) than the saline group (90 ± 3% of the control). In vivo, zinc relieved anemia in 5/6-nephrectomized rats similar to rHuEPO. In vitro, we cultured rat bone marrow cells supplemented with ZnCl2, rHuEPO, or saline. In a 4-day suspension culture, we found that zinc induced erythropoiesis similar to rHuEPO. When rat bone marrow cells were supplement-cultured with zinc, we found that zinc stimulated the production of EPO in the culture medium and that the level of EPO produced was dependent on the concentration of zinc supplemented. The production of EPO via zinc supplementation was involved in the process of erythropoiesis.
Ultrafine Particles from Residential Biomass Combustion: A Review on Experimental Data and Toxicological Response
Authors: Corsini Emanuela , Marinovich Marina , Vecchi Roberta
Published: October 2019

Biomass burning is considered an important source of indoor and outdoor air pollutants worldwide. Due to competitive costs and climate change sustainability compared to fossil fuels, biomass combustion for residential heating is increasing and expected to become the major source of primary particulate matter emission over the next 5–15 years. The understanding of health effects and measures necessary to reduce biomass emissions of harmful compounds is mandatory to protect public health. The intent of this review is to report available data on ultrafine particles (UFPs, i.e., particles with diameter smaller than 100 nm) emitted by residential biomass combustion and their effects on human health (in vitro and in vivo studies). Indeed, as far as we know, papers focusing specifically on UFPs originating from residential biomass combustion and their impact on human health are still lacking.
Adaptive Radiation from a Chromosomal Perspective: Evidence of Chromosome Set Stability in Cichlid Fishes (Cichlidae: Teleostei) from the Barombi Mbo Lake, Cameroon
Authors: Majtánová Zuzana , Indermaur Adrian , Bitja Nyom Arnold Roger , Ráb Petr , Musilova Zuzana
Published: October 2019

Cichlid fishes are the subject of scientific interest because of their rapid adaptive radiation, resulting in extensive ecological and taxonomic diversity. In this study, we examined 11 morphologically distinct cichlid species endemic to Barombi Mbo, the largest crater lake in western Cameroon, namely Konia eisentrauti, Konia dikume, Myaka myaka, Pungu maclareni, Sarotherodon steinbachi, Sarotherodon lohbergeri, Sarotherodon linnellii, Sarotherodon caroli, Stomatepia mariae, Stomatepia pindu, and Stomatepia mongo. These species supposedly evolved via sympatric ecological speciation from a common ancestor, which colonized the lake no earlier than one million years ago. Here we present the first comparative cytogenetic analysis of cichlid species from Barombi Mbo Lake using both conventional (Giemsa staining, C-banding, and CMA3/DAPI staining) and molecular (fluorescence in situ hybridization with telomeric, 5S, and 28S rDNA probes) methods. We observed stability on both macro and micro-chromosomal levels. The diploid chromosome number was 2n = 44, and the karyotype was invariably composed of three pairs of meta/submetacentric and 19 pairs of subtelo/acrocentric chromosomes in all analysed species, with the same numbers of rDNA clusters and distribution of heterochromatin. The results suggest the evolutionary stability of chromosomal set; therefore, the large-scale chromosomal rearrangements seem to be unlikely associated with the sympatric speciation in Barombi Mbo.
Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels
Authors: León-Aparicio Daniel , Salvador Carolina , Aparicio-Trejo Omar Emiliano , Briones-Herrera Alfredo , Pedraza-Chaverri José , Vaca Luis , Sampieri Alicia , Padilla-Flores Teresa , López-González Zinaeli , León-Contreras Juan C , Hernández-Pando Rogelio , Escobar Laura I
Published: October 2019

Hyperpolarization-activated cationic HCN channels comprise four members (HCN1–4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K+) and ammonium into the nephrons. HCN3 is regulated by K+ diets in the kidney. In this work we performed a proteomic analysis of HCN3 expressed in human embryonic kidney cells (HEK293 cells). More than 50% of the interacting proteins belonged to mitochondria. Therefore, we explored the presence of HCN channels in kidney mitochondria. By immunoblotting and immunogold electron microscopy HCN3 protein expression was found in rat kidney mitochondria; it was also confirmed in human kidney. Patch-clamp recordings of renal mitochondria and mitochondria from HEK293 cells overexpressing HCN1, HCN2 and HCN3 channels, stained with MitoTracker Green FM, indicated that only HCN3 could produce inwardly K+ currents that were inhibited by ZD7288, a specific blocker of HCN channels. Furthermore, ZD7288 caused inhibition of the oxygen consumption coupled to ATP synthesis and hyperpolarization of the inner mitochondrial membrane. In conclusion, we show for the first time that pacemaker HCN channels contribute to K+ transport in mitochondria facilitating the activity of the respiratory chain and ATP synthesis by controlling the inner mitochondrial membrane potential.
Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications
Authors: Fernández-Villa Daniel , Aguilar Maria Rosa , Rojo Luis
Published: October 2019

Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications.
Kadaster Knowledge Graph: Beyond the Fifth Star of Open Data
Authors: Ronzhin Stanislav , Folmer Erwin , Maria Pano , Brattinga Marco , Beek Wouter , Lemmens Rob , van’t Veer Rein
Published: October 2019

After more than a decade, the supply-driven approach to publishing public (open) data has resulted in an ever-growing number of data silos. Hundreds of thousands of datasets have been catalogued and can be accessed at data portals at different administrative levels. However, usually, users do not think in terms of datasets when they search for information. Instead, they are interested in information that is most likely scattered across several datasets. In the world of proprietary in-company data, organizations invest heavily in connecting data in knowledge graphs and/or store data in data lakes with the intention of having an integrated view of the data for analysis. With the rise of machine learning, it is a common belief that governments can improve their services, for example, by allowing citizens to get answers related to government information from virtual assistants like Alexa or Siri. To provide high-quality answers, these systems need to be fed with knowledge graphs. In this paper, we share our experience of constructing and using the first open government knowledge graph in the Netherlands. Based on the developed demonstrators, we elaborate on the value of having such a graph and demonstrate its use in the context of improved data browsing, multicriteria analysis for urban planning, and the development of location-aware chat bots.
Effects of Insecticide Stress on Expression of NlABCG Transporter Gene in the Brown Planthopper, Nilaparvata lugens
Authors: Yang Hong , Zhou Cao , Yang Xi-Bin , Long Gui-Yun , Jin Dao-Chao
Published: October 2019

The brown planthopper (BPH), Nilaparvata lugens, is an important pest of rice that severely affects production. Insecticides are an important means of controlling BPH, but their long-term use has led to resistance. To provide insight into BPH responses to insecticide stress, we determined the expression levels of BPH ABCG transporter genes under treatment with thiamethoxam, abamectin, and cyantraniliprole at LC10, LC25, LC50, and LC90. We cloned 13 BPH ABCG transporters, named NlABCG1 to NlABCG13. Conservative domain analysis showed that all 13 transporters have one nucleotide binding domain and one transmembrane domain, typical of semi-molecular transporters. Real-time quantitative PCR showed that thiamethoxam, abamectin, and cyantraniliprole stress increased the expression of some NlABCG transporters gene in BPH. However, after treatment with thiamethoxam at LC25 and abamectin at LC10, there was no significant upregulation of NlABCG. These results indicate that the expression of NlABCG varies in response to stress from different insecticides. These findings provide baseline information for further understanding of the molecular mechanisms of insecticide resistance in BPH.
Surface Energy and Tribology of Electrodeposited Ni and Ni–Graphene Coatings on Steel
Authors: Siddaiah Arpith , Kumar Pankaj , Henderson Artie , Misra Manoranjan , Menezes Pradeep L.
Published: October 2019

Composite electrochemical coatings (CECs) are some of the most widely investigated coatings due to its versatility in tailoring physio-mechanical and tribological properties. The effectiveness of the CECs for tribological applications is dependent on the solid–liquid interfaces. The active and passive nature of the contact boundaries for a CEC with a solid/liquid interface is defined by the surface energy of these boundaries. Unless the effect of surface energy on the tribological properties of the CEC are understood, it is not possible to get a holistic picture on properties, such as corrosion and tribocorrosion. The present study investigates the surface energy of optimized nickel (Ni) and Ni–graphene (Ni–Gr) coatings and their effect on the dynamic friction and wear behavior. It was found that the addition of Gr to the Ni coating in small quantities could decrease the polar component of surface energy significantly than the dispersive component. The presence of Gr in the coating was able to reduce the wear while providing low friction. The Ni–Gr coating exhibited low surface energy that includes weak adhesive forces, which can prevent embedding of the wear particles during sliding.
Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge Crambe tailliezi
Authors: Nguyen Thi-Ngoc-Dung , Feizbakhsh Omid , Sfecci Estelle , Baratte Blandine , Delehouzé Claire , Garcia Adrien , Moulin Corentin , Colas Pierre , Ruchaud Sandrine , Mehiri Mohamed , Bach Stéphane
Published: October 2019

Regulated cell death (RCD) results from the activation of one or more signal transduction modules both in physiological or pathological conditions. It is now established that RCD is involved in numerous human diseases, including cancer. As regulated cell death processes can be modulated by pharmacological tools, the research reported here aims to characterize new marine compounds acting as RCD modulators. Protein kinases (PKs) are key signaling actors in various RCDs notably through the control of either mitosis (e.g., the PKs Aurora A and B) or necroptosis (e.g., RIPK1 and RIPK3). From the primary screening of 27 various extracts of marine organisms collected in the Mediterranean Sea, an extract and subsequently a purified high molecular weight compound dubbed P3, were isolated from the marine sponge Crambe tailliezi and characterized as a selective inhibitor of PKs Aurora A and B. Furthermore, P3 was shown to induce apoptosis and to decrease proliferation and mitotic index of human osteosarcoma U-2 OS cells.
Phlorotannins from Ecklonia cava Attenuates Palmitate-Induced Endoplasmic Reticulum Stress and Leptin Resistance in Hypothalamic Neurons
Authors: Oh Seyeon , Son Myeongjoo , Choi Junwon , Choi Chang Hu , Park Kook Yang , Son Kuk Hui , Byun Kyunghee
Published: October 2019

Leptin resistance in the hypothalamus has an essential role in obesity. Saturated fatty acids such as palmitate bind to Toll-like receptor 4 (TLR4) and lead to endoplasmic reticulum (ER) stress and leptin resistance. In this study, we evaluated whether extracts of Ecklonia cava would attenuate the ER stress induced by palmitate and reduce leptin resistance in hypothalamic neurons and microglia. We added palmitate to these cells to mimic the environment induced by high-fat diet in the hypothalamus and evaluated which of the E. cava phlorotannins—dieckol (DK), 2,7-phloroglucinol-6,6-bieckol (PHB), pyrogallol-phloroglucinol-6,6-bieckol (PPB), or phlorofucofuroeckol-A (PFFA)—had the most potent effect on attenuating leptin resistance. TLR4 and NF-κB expression induced by palmitate was attenuated most effectively by PPB in both hypothalamic neurons and microglia. ER stress markers were increased by palmitate and were attenuated by PPB in both hypothalamic neurons and microglia. Leptin resistance, which was evaluated as an increase in SOCS3 and a decrease in STAT3 with leptin receptor expression, was increased by palmitate and was decreased by PPB in hypothalamic neurons. The culture medium from palmitate-treated microglia increased leptin resistance in hypothalamic neurons and this resistance was attenuated by PPB. In conclusion, PPB attenuated leptin resistance by decreasing ER stress in both hypothalamic neurons and microglia.
Analysis of Road Traffic Accidents in Turkey between 2013 and 2017
Authors: Erenler Ali Kemal , Gümüş Burak
Published: October 2019

Background and objectives: Road traffic accident (RTAs) is one of the top ten leading causes of death worldwide and its incidence is higher in developing countries. In this study, our aim was to determine the characteristics of RTAs in Turkey and make recommendations to reduce mortality and morbidity related to RTAs. Material and Methods: We obtained our data, which cover the years 2013 to 2017, from the database accessible at the official website of the Turkish Statistical Institute, which permits the use of its data for research purposes. The chi-square test was used for statistical analysis, and the percentage distribution and odds ratios were calculated. Results: In the study period, a total of 697,957 RTAs occurred in Turkey. A total of 1,168,121 individuals have been wounded and 3534 of them have lost their lives. The majority of RTAs occurred on weekends and in summer months. Male individuals are more likely to be exposed to death and injuries related to accidents. When the vehicle type is considered, motorcycle drivers are under more risk for RTAs. RTAs are more likely to occur in rural areas. Conclusion: Male individuals and motorcyclists are under a great risk for RTAs. Strict laws are mandatory in order to reduce morbidity and mortality related to RTAs. Additionally, educational efforts must focus on two-wheelers and tractor drivers, particularly in developing countries.
Three-Dimensional Bioprinting of Functional Skeletal Muscle Tissue Using Gelatin Methacryloyl-Alginate Bioinks
Authors: Seyedmahmoud Rasoul , Çelebi-Saltik Betül , Barros Natan , Nasiri Rohollah , Banton Ethan , Shamloo Amir , Ashammakhi Nureddin , Dokmeci Mehmet Remzi , Ahadian Samad
Published: October 2019

Skeletal muscle tissue engineering aims to fabricate tissue constructs to replace or restore diseased or injured skeletal muscle tissues in the body. Several biomaterials and microscale technologies have been used in muscle tissue engineering. However, it is still challenging to mimic the function and structure of the native muscle tissues. Three-dimensional (3D) bioprinting is a powerful tool to mimic the hierarchical structure of native tissues. Here, 3D bioprinting was used to fabricate tissue constructs using gelatin methacryloyl (GelMA)-alginate bioinks. Mechanical and rheological properties of GelMA-alginate hydrogels were characterized. C2C12 myoblasts at the density 8 × 106 cells/mL were used as the cell model. The effects of alginate concentration (0, 6, and 8% (w/v)) and crosslinking mechanism (UV crosslinking or ionic crosslinking with UV crosslinking) on printability, cell viability, proliferation, and differentiation of bioinks were studied. The results showed that 10% (w/v) GelMA-8% (w/v) alginate crosslinked using UV light and 0.1 M CaCl2 provided the optimum niche to induce muscle tissue formation compared to other hydrogel compositions. Furthermore, metabolic activity of cells in GelMA bioinks was improved by addition of oxygen-generating particles to the bioinks. It is hoped that such bioprinted muscle tissues may find wide applications in drug screening and tissue regeneration.
Mineral Fibres and Asbestos Bodies in Human Lung Tissue: A Case Study
Authors: Di Giuseppe Dario , Zoboli Alessandro , Vigliaturo Ruggero , Gieré Reto , Bonasoni Maria Paola , Sala Orietta , Gualtieri Alessandro Francesco
Published: October 2019

One of the open questions regarding the asbestos problem is the fate of the mineral fibres in the body once inhaled and deposited in the deep respiratory system. In this context, the present paper reports the results of an electron microscopy study of both mineral fibres and asbestos bodies found in the lung tissue of a patient who died of malignant mesothelioma due to past occupational exposure. In concert with previous in vivo animal studies, our data provide evidence that amphibole asbestos fibres are durable in the lungs, whereas chrysotile fibres are transformed into a silica-rich product, which can be easily cleared. Amphibole fibres recovered from samples of tissue of the deceased display a high degree of crystallinity but also show a very thin amorphous layer on their surface; 31% of the fibres are coated with asbestos bodies consisting of a mixture of ferroproteins (mainly ferritin). Here, we propose an improved model for the coating process. Formation of a coating on the fibres is a defence mechanism against fibres that are longer than 10 µm and thinner than 0.5 µm, which macrophages cannot engulf. The mature asbestos bodies show signs of degradation, and the iron stored in ferritin may be released and potentially increase oxidative stress in the lung tissue.
Schizandrin Protects against OGD/R-Induced Neuronal Injury by Suppressing Autophagy: Involvement of the AMPK/mTOR Pathway
Authors: Wang Guangyun , Wang Tiezheng , Zhang Yuanyuan , Li Fang , Yu Boyang , Kou Junping
Published: October 2019

The neuroprotective role of schizandrin (SA) in cerebral ischemia-reperfusion (I/R) was recently highlighted. However, whether SA plays a regulatory role on autophagy in cerebral I/R injury is still unclear. This study aimed to explore whether the neuroprotective mechanisms of SA were linked to its regulation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/autophagy pathway in vivo and in vitro. The present study confirmed that SA significantly improved oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced PC12 cells injury. The results of immunoblotting and confocal microscope showed that SA decreased autophagy in OGD/R-injured PC12 cells, which was reflected by the decreased Beclin-1 and LC3-II expression, autophagy flux level, and LC3 puncta formation. In addition, the autophagy inducer rapamycin partially prevented the effects of SA on cell viability and autophagy after OGD/R, whereas the autophagy inhibitor 3-methyladenine (3-MA) exerted the opposite effect. The results of Western blotting showed that SA markedly decreased the phosphorylation of AMPK (p-AMPK), whereas the phosphor-mTOR (p-mTOR) levels increased in the presence of OGD/R insult. Furthermore, pretreatment with the AMPK inducer AICAR partially reversed the protective effects and autophagy inhibition of SA. However, AMPK inhibitor Compound C pretreatment further promoted the inhibition of SA on autophagy induction and cell damage induced by OGD/R. Taken together, these findings demonstrate that SA protects against OGD/R insult by inhibiting autophagy through the regulation of the AMPK-mTOR pathway and that SA may have therapeutic value for protecting neurons from cerebral ischemia.
Bimodular Antiparallel G-Quadruplex Nanoconstruct with Antiproliferative Activity
Authors: Antipova Olga , Samoylenkova Nadezhda , Savchenko Ekaterina , Zavyalova Elena , Revishchin Alexander , Pavlova Galina , Kopylov Alexey
Published: October 2019

Oligonucleotides with an antiproliferative activity for human cancer cells have attracted attention over the past decades; many of them have a G-quadruplex structure (GQ), and a cryptic target. In particular, DNA oligonucleotide HD1, a minimal GQ, could inhibit proliferation of some cancer cell lines. The HD1 is a 15-nucleotide DNA oligonucleotide that folds into a minimal chair-like monomolecular antiparallel GQ structure. In this study, for eight human cancer cell lines, we have analyzed the antiproliferative activities of minimal bimodular DNA oligonucleotide, biHD1, which has two HD1 modules covalently linked via single T-nucleotide residue. Oligonucleotide biHD1 exhibits a dose-dependent antiproliferative activity for lung cancer cell line RL-67 and cell line of central nervous system cancer U87 by MTT-test and Ki-67 immunoassay. The study of derivatives of biHD1 for the RL-67 and U87 cell lines revealed a structure-activity correlation of GQ folding and antiproliferative activity. Therefore, a covalent joining of two putative GQ modules within biHD1 molecule provides the antiproliferative activity of initial HD1, opening a possibility to design further GQ multimodular nanoconstructs with antiproliferative activity—either as themselves or as carriers.
Two New AChE Inhibitors Isolated from Li Folk Herb Heilaohu “Kadsura coccinea” Stems
Authors: Huang Sheng Zhuo , Duan Lin Ping , Wang Hao , Mei Wen Li , Dai Hao Fu
Published: October 2019

Two new triterpenoids, named kadsuricoccins A and B, together with three known ones, were isolated from the Li folk herb Heilaohu, the stems of Kadsura coccinea (Lem.) A. C. Smith, which was used for food and as a healthy supplement. Their structures were elucidated by comprehensive analyses of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. To search healthy components, an acetylcholinesterase (AChE) inhibitory activity test by Ellman’s Method was conducted, kadsuricoccins A and B showed activity with the AChE inhibit index (AII) up to 68.96% ± 0.19% and 57.8% ± 0.11% at 94 nM (compared with positive control tacrine AII 79.80% ± 0.20%, 9.4 nM), respectively.
Exploring New Structural Features of the 18β-Glycyrrhetinic Acid Scaffold for the Inhibition of Anaplastic Lymphoma Kinase
Authors: Cai Dong , Zhang ZhiHua , Chen Yu , Zhang YanYan , Sun YuQi , Gong YiXia
Published: October 2019

Novel 18β-glycyrrhetinic acid derivatives possessing a carbamate moiety and structurally similar ester derivatives were developed and evaluated for their efficacy as antitumor inhibitors. In the cellular assays, most of the N-substituted carbamate derivatives at the C3-position exhibited potent activities. The results of SAR investigation revealed that the introduction of the morpholine group at the C30-COOH led to a significant loss of the inhibitory potency. Among the ester derivatives, the ester group at C3-position also determined a noticeable reduction in the efficacy. Compound 3j exhibited the most prominent antiproliferative activity against six human cancer cells (A549, HT29, HepG2, MCF-7, PC-3, and Karpas299). Furthermore, compound 3j exerted a moderate inhibiting effect on the ALK. The results of molecular docking analyses suggested that it could bind well to the active site of the receptor ALK, which was consistent with the biological data. These results might inspire further structural optimization of 18β-glycyrrhetinic acid aiming at the development of potent antitumor agents. The structures 4d, 4g, 4h, 4j, and 4n were studied by X-ray crystallographic analyses.