bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochastic Modeling and Optimal Time-Frequency Estimation of Task-Related HRV
Authors: Anderson Rachele , Jönsson Peter , Sandsten Maria
Published: November 2019

In this paper, we propose a novel framework for the analysis of task-related heart rate variability (HRV). Respiration and HRV are measured from 92 test participants while performing a chirp-breathing task consisting of breathing at a slowly increasing frequency under metronome guidance. A non-stationary stochastic model, belonging to the class of Locally Stationary Chirp Processes, is used to model the task-related HRV data, and its parameters are estimated with a novel inference method. The corresponding optimal mean-square error (MSE) time-frequency spectrum is derived and evaluated both with the individually estimated model parameters and the common process parameters. The results from the optimal spectrum are compared to the standard spectrogram with different window lengths and the Wigner-Ville spectrum, showing that the MSE optimal spectral estimator may be preferable to the other spectral estimates because of its optimal bias and variance properties. The estimated model parameters are considered as response variables in a regression analysis involving several physiological factors describing the test participants’ state of health, finding a correlation with gender, age, stress, and fitness. The proposed novel approach consisting of measuring HRV during a chirp-breathing task, a corresponding time-varying stochastic model, inference method, and optimal spectral estimator gives a complete framework for the study of task-related HRV in relation to factors describing both mental and physical health and may highlight otherwise overlooked correlations. This approach may be applied in general for the analysis of non-stationary data and especially in the case of task-related HRV, and it may be useful to search for physiological factors that determine individual differences.
Fetal Megacystis: A New Morphologic, Immunohistological and Embriogenetic Approach
Authors: Puzzo Lidia , Giunta Giuliana , Caltabiano Rosario , Cianci Antonio , Salvatorelli Lucia
Published: November 2019

Congenital anomalies of the kidney and urinary tract (CAKUT) include isolated kidney malformations and urinary tract malformations. They have also been reported in Prune-Belly syndrome (PBS) and associated genetic syndromes, mainly 13, 18 and 21 trisomy. The AA focuses on bladder and urethral malformations, evaluating the structural and histological differences between two different cases of megacystis. Both bladders were examined by routine prenatal ultrasound screening and immunohistochemistry, comparing the different expression of smooth muscular actin (SMA), S100 protein and WT1c in megacystis and bladders of normal control from fetuses of XXI gestational age. Considering the relationship between the enteric nervous system and urinary tract development, the AA evaluated S100 and WT1c expression both in bladder and bowel muscular layers. Both markers were not expressed in the bladder and bowel of PBS associated with anencephaly. In conclusion, megacystis could be considered only a macroscopic definition, concerning the size of the fetal bladder rather than the embryologic origin; it may be a single or multiple malformation; the possible association with the bowel and/or encephalic malformations will decide the outcome and prognosis in fetal megacystis.
Solvothermal Synthesis of Size-Controlled Monodispersed Superparamagnetic Iron Oxide Nanoparticles
Authors: Chen Yongpeng , Zhang Jianguo , Wang Zhixin , Zhou Zunning
Published: November 2019

Superparamagnetic iron oxide nanoparticles are of great interest in magnetic targeted drug delivery due to their unique properties. In this paper, size-controlled superparamagnetic iron oxide nanoparticles were synthesized in an ethylene glycol/diethylene glycol (EG/DEG) binary solvent system via a facile solvothermal method. X-ray diffraction (XRD), a scanning electron microscope (SEM), and a vibrating sample magnetometer (VSM) were used to confirm that the prepared samples were superparamagnetic Fe 3 O 4 nanospheres. When the V EG / V DEG was varied from 100/0 to 80/20, 60/40, and 40/60, the average diameters of the resulting Fe 3 O 4 nanospheres were approximately 700, 500, 300, and 100 nm, respectively. In addition, the saturation magnetization ( M s ) of Fe 3 O 4 nanoparticles with a size of 100, 300, 500, and 700 nm was 72.14, 75.94, 80.28, and 85.41 emu/g, and the corresponding remanent magnetization ( M r ) was 3.34, 3.97, 3.26, and 4.28 emu/g, respectively. The relevant formation mechanisms of Fe 3 O 4 nanoparticles are proposed at the end. These superparamagnetic Fe 3 O 4 nanoparticles with high saturation magnetization may have use as targeted drug carriers.
Optimization of Triterpene Saponins Mixture with Antiproliferative Activity
Authors: Tatia Rodica , Zalaru Christina , Craciunescu Oana , Moldovan Lucia , Oancea Anca , Calinescu Ioan
Published: November 2019

In this study, three of the saponins present in leaves of Hedera helix L., α-hederin, hederagenin, and hederacoside C were studied for their antiproliferative activity. The three saponins were analyzed in different concentrations by in vitro tests on normal fibroblasts cells and cervix ephitelial tumor cells. Determination of cytotoxicity and antitumor effects was performed using the MTT method. From the tested saponins, α-hederin was biocompatible in normal fibroblasts cells at concentrations between 2–10 μg/mL. Its antiproliferative activity was exerted in the concentration range of 10–400 μg/mL in cervix ephitelial tumor cells. Similarly, hederagenin presented antiproliferative activity at concentrations between 25–400 μg/mL. In turn, hederacoside C was shown to be noncytotoxic in normal fibroblasts and cervix ephitelial tumor cell culture at all the tested concentrations. The obtained experimental results were analyzed by “Mixture design”, a specialized form of the response surface method (RSM) provided by the Design Expert 11 software, and the optimal composition of obtained saponins mixture was selected and verified in vitro for antiproliferative activity. The results showed that an optimal saponins mixture has the potential to be used in pharmacological applications.
Detection and Removal of Moving Object Shadows Using Geometry and Color Information for Indoor Video Streams
Authors: Abdusalomov Akmalbek , Whangbo Taeg Keun
Published: November 2019

The detection and removal of moving object shadows is a challenging issue. In this article, we propose a new approach for accurately removing shadows on modern buildings in the presence of a moving object in the scene. Our approach is capable of achieving good performance when addressing multiple shadow problems, by reducing background surface similarity and ghost artifacts. First, a combined contrast enhancement technique is applied to the input frame sequences to produce high-quality output images for indoor surroundings with an artificial light source. After obtaining suitable enhanced images, segmentation and noise removal filtering are applied to create a foreground mask of the possible candidate moving object shadow regions. Subsequently, geometry and color information are utilized to remove detected shadow pixels that incorrectly include the foreground mask. Here, experiments show that our method correctly detects and removes shadowed pixels in object tracking tasks, such as in universities, department stores, or several indoor sports games.
β-Nitroacrylates: New Key Precursors of Indole-2-Carboxylates via Fischer Indole Synthesis
Authors: Gabrielli Serena , Panmand Deepak , Ballini Roberto , Palmieri Alessandro
Published: November 2019

Indole 2-carboxylates are very important scaffolds that are widely investigated for their activities and are used as key intermediates of biologically active molecules. Herein, we report a new procedure for the preparation of this class of derivatives, via Fischer indole synthesis, starting from β-nitroacrylates and arylhydrazines. The protocol permits the production of the title targets in satisfactory overall yields, avoids any wasteful aqueous work-up, and has with evident advantages from a sustainability point of view.
Analysis of Protein–Receptor Interactions on an Example of Leptin–Leptin Receptor Interaction Using the Resonant Recognition Model
Authors: Cosic Irena , Paspaliaris Vasilis , Cosic Drasko
Published: November 2019

Obesity is a medical condition in which excess body fat may have a negative effect on health and lifestyle, and it is becoming an increasing problem within modern society. Leptin is the key protein that regulates body energy balance by inhibiting hunger, and it could potentially be used in treatment of obesity and overweight. Here, we applied our own Resonant Recognition Model, which is capable of analyzing the selectivity of any protein–receptor interaction on an example of leptin–leptin receptor. We have identified a specific characteristic parameter for leptin activity through the leptin receptor, and this parameter could be used in development of new treatments for obesity.
Effect of Chromatographic Conditions on Supercoiled Plasmid DNA Stability and Bioactivity
Authors: Azevedo G.M. , Valente J.F.A. , Sousa A. , Pedro A.Q. , Pereira P. , Sousa F. , Queiroz J.A.
Published: November 2019

The dysfunction of the tumor suppressor gene TP53 has been associated with the pathogenesis of the majority of the cases of cancer reported to date, leading the cell to acquire different features known as the cancer hallmarks. In normal situations, the protein p53 protects the cells against tumorigenesis. By detecting metabolic stress or DNA damage in response to stress, p53 can lead the cell to senescence, autophagy, cell cycle arrest, DNA repair, and apoptosis. Thus, in the case of p53 mutations, it is reasonable to assume that the reestablishment of its function, may restrain the proliferation of cancer cells. The concept of cancer gene therapy can be based on this assumption, and suitable biotechnological approaches must be explored to assure the preparation of gene-based biopharmaceuticals. Although numerous procedures have already been established to purify supercoiled plasmid DNA (sc pDNA), the therapeutic application is highly dependent on the biopharmaceutical’s activity, which can be affected by the chromatographic conditions used. Thus, the present work aims at comparing quality and in vitro activity of the supercoiled (sc) isoform of the p53 encoding plasmid purified by three different amino acids-based chromatographic strategies, involving histidine–agarose, arginine–macroporous, and histidine–monolith supports. The B-DNA topology was maintained in all purified pDNA samples, but their bioactivity, related to the induction of protein p53 expression and apoptosis in cancer cells, was higher with arginine–macroporous support, followed by histidine–monolith and histidine–agarose. Despite the purity degree of 92% and recovery yield of 43% obtained with arginine–macroporous, the sc pDNA sample led to a higher expression level of the therapeutic p53 protein (58%) and, consequently, induced a slightly higher apoptotic effect (27%) compared with sc pDNA samples obtained with histidine–monolithic support (26%) and histidine–agarose support (24%). This behavior can be related to the mild chromatographic conditions used with arginine–macroporous support, which includes the use of low salt concentrations, at neutral pH and lower temperatures, when compared to the high ionic strength of ammonium sulfate and acidic pH used with histidine-based supports. These results can contribute to field of biopharmaceutical preparation, emphasizing the need to control several experimental conditions while adapting and selecting the methodologies that enable the use of milder conditions as this can have a significant impact on pDNA stability and biological activity.
Reinforcement Learning-Based Anti-Jamming in Networked UAV Radar Systems
Authors: Wu Qinhao , Wang Hongqiang , Li Xiang , Zhang Bo , Peng Jinlin
Published: November 2019

The networked unmanned aerial vehicle (UAV) radar system may exploit inter-UAV cooperation for enhancing information acquisition capabilities, meanwhile its inter-UAV communications may be interfered with by external jammers. This paper is devoted to quantifying and optimizing the anti-jamming performance of networked UAV radar systems in adversarial electromagnetic environments. Firstly, instead of using the conventional metric of signal-to-interference ratio (SIR), this paper explores use of the theory of radar information representation as the basis of evaluating the information acquisition capabilities of the networked UAV radar systems. Secondly, this paper proposes a modified Q-Learning method based on double greedy algorithm to optimize the anti-jamming performance of the networked UAV radar systems, through joint programming in the frequency-motion-antenna domain. Simulation results prove the effectiveness of the algorithm in two different networking scenarios.
Influence of Polymorphisms of DNA Repair and GST Genes on Genotoxic Damage and Mutagen Sensitivity in Workers Occupationally Exposed to Very Low Doses of Ionizing Radiation
Authors: Stufano Angela , Chiarappa Patrizia , Bagnulo Rosanna , Drago Ignazio , Rapisarda Venerando , Ledda Caterina , Vimercati Luigi , De Benedictis Leonarda , Resta Nicoletta , Soleo Leonardo , Lovreglio Piero
Published: November 2019

The study investigated the influence of genetic polymorphisms of the enzymes for DNA repair and detoxification of reactive intermediates on spontaneous and bleomycin-induced (BLM) genotoxic damage in 43 workers exposed to very low doses of ionizing radiation (IR) (mean cumulative dose 5.31 mSv) and 43 subjects with no occupational exposure to IR (controls). In all the subjects examined, the frequency of chromosome aberrations (CAs) and micronuclei (MN), both spontaneous and BLM-induced, the Comet assay parameters (tail intensity), the genotypic variants of the DNA repair enzymes XRCC1 (Arg194Trp, Arg280His, Arg399Gln), XRCC3 (Thr241Met), XPD (Lys751Gln), and of the detoxification enzymes GSTM1 and GSTT1 (null genotype) and BLMH (A1450G) were determined. Among the biomarkers considered, only the frequency of total CAs (p < 0.05), and in particular of chromosome breaks (p < 0.01), was found to be significantly higher in the exposed workers than the controls. The frequency of spontaneous MN was higher in subjects with at least one allelic variant in XRCC1 than in carriers of the wild-type, but again only in exposed workers (p = 0.046). Linear regression analysis showed a positive dependency of the frequency of spontaneous chromosome breaks on occupational exposure, and a dependency of the frequency of BLM-induced MN negative on occupational exposure and positive on alcohol consumption and the null GSTM1 genotype. In conclusion, the frequency of chromosome breaks seems to be a useful cytogenetic biomarker for exposure to very low doses of IR, while only the combined effect of different gene variants or genetic, occupational, and lifestyle habits factors seems to be able to modulate the genotoxic effect of very low doses of IR.
Improving Bibliographic Coupling with Category-Based Cocitation
Authors: Liu Rey-Long , Hsu Chih-Kai
Published: November 2019

Bibliographic coupling (BC) is a similarity measure for scientific articles. It works based on an expectation that two articles that cite a similar set of references may focus on related (or even the same) research issues. For analysis and mapping of scientific literature, BC is an essential measure, and it can also be integrated with different kinds of measures. Further improvement of BC is thus of both practical and technical significance. In this paper, we propose a novel measure that improves BC by tackling its main weakness: two related articles may still cite different references. Category-based cocitation (category-based CC) is proposed to estimate how these different references are related to each other, based on the assumption that two different references may be related if they are cited by articles in the same categories about specific topics. The proposed measure is thus named BCCCC (Bibliographic Coupling with Category-based Cocitation). Performance of BCCCC is evaluated by experimentation and case study. The results show that BCCCC performs significantly better than state-of-the-art variants of BC in identifying highly related articles, which report conclusive results on the same specific topics. An experiment also shows that BCCCC provides helpful information to further improve a biomedical search engine. BCCCC is thus an enhanced version of BC, which is a fundamental measure for retrieval and analysis of scientific literature.
Growth Rate of Gravity Wave Amplitudes Observed in Sodium Lidar Density Profiles and Nightglow Image Data
Authors: Vargas Fabio , Yang Guotao , Batista Paulo , Gobbi Delano
Published: November 2019

Amplitude growth rates of quasi-monochromatic gravity waves were estimated and compared from multiple instrument measurements carried out in Brazil. Gravity wave parameters, such as the wave amplitude and growth rate in distinct altitudes, were derived from sodium lidar density and nightglow all-sky images. Lidar observations were carried out in São Jose dos Campos (23 ∘ S, 46 ∘ W) from 1994 to 2004, while all-sky imagery of multiple airglow layers was conducted in Cachoeira Paulista (23 ∘ S, 45 ∘ W) from 1999–2000 and 2004–2005. We have found that most of the measured amplitude growth rates indicate dissipative behavior for gravity waves identified in both lidar profiles and airglow image datasets. Only a small fraction of the observed wave events (4% imager; 9% lidar) are nondissipative (freely propagating waves). Our findings also show that imager waves are strongly dissipated within the mesosphere and lower thermosphere region (MLT), decaying in amplitude in short distances (<12 km), while lidar waves tend to maintain a constant amplitude within that region. Part of the observed waves (16% imager; 36% lidar) showed unchanging amplitude with altitude (saturated waves). About 51.6% of the imager waves present strong attenuation (overdamped waves) in contrast with 9% of lidar waves. The general saturated or damped behavior is consistent with diffusive filtering processes imposing limits to amplitude growth rates of the observed gravity waves.
Impacts of Thinning Aircraft Observations on Data Assimilation and Its Prediction during Typhoon Nida (2016)
Authors: Gao Yudong , Xiao Hui , Jiang Dehai , Wan Qilin , Chan Pak Wai , Hon Kai Kwong , Deng Guo
Published: November 2019

High frequency aircraft observations from the Government Flying Service of the Hong Kong Government, penetrating a tropical cyclone at low altitude over the South China Sea, were thinned by arithmetic means over different time intervals to identify structures of tropical cyclone at different scales. It is found that the thinning process can reduce serial correlation in observational errors and enhance the representation of aircraft observations. Assimilation experiments demonstrate that aircraft observations can improve the track and intensity forecasts of Typhoon Nida (2016). The changes in dynamic structures indicate that the imbalance generated from assimilating aircraft observations at the sub-grid scale can be alleviated by using longer time intervals of the arithmetic mean. Assimilating aircraft observations at the grid scale achieves optimal forecasts based on verifications against independent observations and investigations of environmental and ventilation flows. In addition, it is indicated that decreasing the quality control threshold and changing the observational error of aircraft observations in the data assimilation can reduce the representation errors.
Proteomic Response of Pseudomonas putida KT2440 to Dual Carbon-Phosphorus Limitation during mcl-PHAs Synthesis
Authors: Możejko-Ciesielska Justyna , Serafim Luísa S.
Published: November 2019

Pseudomonas putida KT2440, one of the best characterized pseudomonads, is a metabolically versatile producer of medium-chain-length polyhydroxyalkanoates (mcl-PHAs) that serves as a model bacterium for molecular studies. The synthesis of mcl-PHAs is of great interest due to their commercial potential. Carbon and phosphorus are the essential nutrients for growth and their limitation can trigger mcl-PHAs’ production in microorganisms. However, the specific molecular mechanisms that drive this synthesis in Pseudomonas species under unfavorable growth conditions remain poorly understood. Therefore, the proteomic responses of Pseudomonas putida KT2440 to the limited carbon and phosphorus levels in the different growth phases during mcl-PHAs synthesis were investigated. The data indicated that biopolymers’ production was associated with the cell growth of P. putida KT2440 under carbon- and phosphorus-limiting conditions. The protein expression pattern changed during mcl-PHAs synthesis and accumulation, and during the different physiological states of the microorganism. The data suggested that the majority of metabolic activities ceased under carbon and phosphorus limitation. The abundance of polyhydroxyalkanoate granule-associated protein (PhaF) involved in PHA synthesis increased significantly at 24 and 48 h of the cultivations. The activation of proteins belonging to the phosphate regulon was also detected. Moreover, these results indicated changes in the protein profiles related to amino acids metabolism, replication, transcription, translation, stress response mechanisms, transport or signal transduction. The presented data allowed the investigation of time-course proteome alterations in response to carbon and phosphorus limitation, and PHAs synthesis. This study provided information about proteins that can be potential targets in improving the efficiency of mcl-PHAs synthesis.
Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren
Authors: Castañeda-Zegarra Sergio , Huse Camilla , Røsand Øystein , Sarno Antonio , Xing Mengtan , Gago-Fuentes Raquel , Zhang Qindong , Alirezaylavasani Amin , Werner Julia , Ji Ping , Liabakk Nina-Beate , Wang Wei , Bjørås Magnar , Oksenych Valentyn
Published: November 2019

Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes, and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. The Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factor subunits X-ray repair cross-complementing group 4 (XRCC4), XRCC4-like factor (XLF), and DNA ligase 4 (Lig4). Accessory factors might be dispensable for the process, depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced a frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as the wild type controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.
Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients
Authors: Zerr Inga , Villar-Piqué Anna , Schmitz Vanda Edit , Poleggi Anna , Pocchiari Maurizio , Sánchez-Valle Raquel , Calero Miguel , Calero Olga , Baldeiras Inês , Santana Isabel , Kovacs Gabor G. , Llorens Franc , Schmitz Matthias
Published: November 2019

The exploration of accurate diagnostic markers for differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous study on cerebrospinal fluid (CSF)-mitochondrial malate dehydrogenase 1 (MDH1) in sporadic Creutzfeldt–Jakob disease (sCJD) patients revealed a highly significant upregulation of MDH1. Here, we measured the CSF levels of MDH1 via enzyme-linked immunosorbent assay in a cohort of rare genetic prion disease cases, such as genetic CJD (gCJD) cases, exhibiting the E200K, V210I, P102L (Gerstmann–Sträussler–Scheinker syndrome (GSS)), or D178N (fatal familial insomnia (FFI)) mutations in the PRNP. Interestingly, we observed enhanced levels of CSF-MDH1 in all genetic prion disease patients compared to neurological controls (without neurodegeneration). While E200K and V210I carriers showed highest levels of MDH1 with diagnostic discrimination from controls of 0.87 and 0.85 area under the curve (AUC), FFI and GSS patients exhibited only moderately higher CSF-MDH1 levels than controls. An impact of the PRNP codon 129 methionine/valine (MV) genotype on the amount of MDH1 could be excluded. A correlation study of MDH1 levels with other neurodegenerative marker proteins revealed a significant positive correlation between CSF-MDH1 concentration with total tau (tau) but not with 14-3-3 in E200K, as well as in V210I patients. In conclusion, our study indicated the potential use of MDH1 as marker for gCJD patients which may complement the current panel of diagnostic biomarkers.
UV-Vis Spectroelectrochemistry of Oleuropein, Tyrosol, and p-Coumaric Acid Individually and in an Equimolar Combination. Differences in LC-ESI-MS2 Profiles of Oxidation Products and Their Neuroprotective Properties
Authors: Lambert de Malezieu Morgane , Ferron Solenn , Sauvager Aurélie , Courtel Patricia , Ramassamy Charles , Tomasi Sophie , Abasq Marie-Laurence
Published: November 2019

Major phenolic compounds from olive oil (ArOH-EVOO), oleuropein (Ole), tyrosol (Tyr), and p-coumaric acid (p-Cou), are known for their antioxidant and neuroprotective properties. We previously demonstrated that their combination could potentiate their antioxidant activity in vitro and in cellulo. To further our knowledge of their electron-transfer properties, Ole, Tyr, and p-Cou underwent a spectroelectrochemical study, performed either individually or in equimolar mixtures. Two mixtures (Mix and Mix-seq) were prepared in order to determine whether distinct molecules could arise from their simultaneous or sequential oxidation. The comparison of Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry (LC-ESI-MS2) profiles highlighted the presence of specific oxidized products found in the mixes. We hypothesized that they derived from the dimerization between Tyr and Ole or p-Cou, which have reacted either in their native or oxidized forms. Moreover, Ole regenerates when the Mix undergoes oxidation. Our study also showed significant neuroprotection by oxidized Ole and oxidized Mix against H2O2 toxicity on SK-N-SH cells, after 24 h of treatment with very low concentrations (1 and 5 nM). This suggests the putative relevant role of oxidized Ole products to protect or delay neuronal death.
Higher Serum Melatonin Levels during the First Week of Malignant Middle Cerebral Artery Infarction in Non-Surviving Patients
Authors: Lorente Leonardo , Martín María , Abreu-González Pedro , Sabatel Rafael , Ramos Luis , Argueso Mónica , Solé-Violán Jordi , Cáceres Juan , Jiménez Alejandro , García-Marín Victor
Published: November 2019

Objective: The activation of different physiopathological pathways (neuroinflammation, apoptosis, and oxidation) can lead to secondary brain injury in ischemic stroke, and in animal models the administration of melatonin has reduced that secondary injury. Lower levels of serum melatonin were found at the time of admission of cerebral infarction in surviving patients than in non-surviving patients. Thus, we carried out this prospective and observational study with the aim of exploring serum melatonin levels in the first week of a malignant middle cerebral artery infarction (MMCAI) in surviving and non-surviving patients, and to explore the capacity of those levels to predict mortality. Methods: Patients with severe MMCAI, defined as computed tomography showing acute infarction in more than 50% of the territory and Glasgow Coma Scale (GCS) lower than 9, were included in the study. We measured serum melatonin concentrations at days 1, 4, and 8 of MMCAI. Mortality at 30 days was the endpoint of our study. Results: Non-surviving patients (n = 34) compared to surviving patients (n = 34) showed higher serum melatonin levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.001) of MMCAI. Serum melatonin concentrations at days 1, 4, and 8 of MMCAI had an area under the curve (AUC) (95% confidence interval (CI)) in the prediction of mortality of 0.89 (0.80–0.96; p < 0.001), 0.81 (0.68–0.91; p < 0.001), and 0.82 (0.68–0.92; p < 0.001), respectively. Conclusions: The novel findings of our study were that serum melatonin levels in the first week of MMCAI were higher in non-surviving patients, and were able to predict mortality.
Radiosensitization of Non-Small Cell Lung Cancer Cells by the Plk1 Inhibitor Volasertib Is Dependent on the p53 Status
Authors: Van den Bossche Jolien , Domen Andreas , Peeters Marc , Deben Christophe , De Pauw Ines , Jacobs Julie , De Bruycker Sven , Specenier Pol , Pauwels Patrick , Vermorken Jan Baptist , Lardon Filip , Wouters An
Published: November 2019

Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division, is highly expressed in non-small cell lung cancer (NSCLC) making it an interesting drug target. We examined the in vitro therapeutic effects of volasertib, a Plk1 inhibitor, in combination with irradiation in a panel of NSCLC cell lines with different p53 backgrounds. Pretreatment with volasertib efficiently sensitized p53 wild type cells to irradiation. Flow cytometric analysis revealed that significantly more cells were arrested in the G2/M phase of the cell cycle after the combination therapy compared to either treatment alone (p < 0.005). No significant synergistic induction of apoptotic cell death was observed, but, importantly, significantly more senescent cells were detected when cells were pretreated with volasertib before irradiation compared to both monotherapies alone (p < 0.001), especially in cells with functional p53. Consequently, while most cells with functional p53 showed permanent growth arrest, more p53 knockdown/mutant cells could re-enter the cell cycle, resulting in colony formation and cell survival. Our findings assign functional p53 as a determining factor for the observed radiosensitizing effect of volasertib in combination with radiotherapy for the treatment of NSCLC.
Long-Term Fatigue and Cognitive Disorders in Breast Cancer Survivors
Authors: Joly Florence , Lange Marie , Dos Santos Melanie , Vaz-Luis Ines , Di Meglio Antonio
Published: November 2019

Survivors of early-stage breast cancer may report treatment-related side effects that persist for several years after the end of primary treatment. Among these, fatigue and cognitive disorders are frequent complaints and can negatively impact quality of life. Cancer-related fatigue is a very prevalent and distressing long-term side effect among breast cancer survivors that typically improves after completion of treatment, although many patients report severe fatigue several years post-treatment. Cognitive disorders are also common among survivors of breast cancer, especially if treated with chemotherapy. These symptoms are usually mild-to-moderate and often transient. Cognitive recovery is frequently observed within months or a few years after completion of chemotherapy or endocrine therapy. However, some breast cancer survivors may have persistent cognitive difficulties. Several types of interventions have proved to be beneficial in reducing cancer-related fatigue and cognitive difficulties. Most of these interventions for cancer-related fatigue are thought to be effective by reducing inflammation or disrupting pro-inflammatory circuits. Further studies are needed on cognitive management that has showed promising results. This narrative review summarizes the state of the art regarding long-term fatigue and cognitive disorders in patients with early breast cancer, describing prevalence, impact, pathophysiology, and risk factors, and focusing on available interventions.
Endogenous Roles of Mammalian Flavin-Containing Monooxygenases
Authors: Phillips Ian R. , Shephard Elizabeth A.
Published: November 2019

Flavin-containing monooxygenases (FMOs) catalyze the oxygenation of numerous foreign chemicals. This review considers the roles of FMOs in the metabolism of endogenous substrates and in physiological processes, and focuses on FMOs of human and mouse. Tyramine, phenethylamine, trimethylamine, cysteamine, methionine, lipoic acid and lipoamide have been identified as endogenous or dietary-derived substrates of FMOs in vitro. However, with the exception of trimethylamine, the role of FMOs in the metabolism of these compounds in vivo is unclear. The use, as experimental models, of knockout-mouse lines deficient in various Fmo genes has revealed previously unsuspected roles for FMOs in endogenous metabolic processes. FMO1 has been identified as a novel regulator of energy balance that acts to promote metabolic efficiency, and also as being involved in the biosynthesis of taurine, by catalyzing the S-oxygenation of hypotaurine. FMO5 has been identified as a regulator of metabolic ageing and glucose homeostasis that apparently acts by sensing or responding to gut bacteria. Thus, FMOs do not function only as xenobiotic-metabolizing enzymes and there is a risk that exposure to drugs and environmental chemicals that are substrates or inducers of FMOs would perturb the endogenous functions of these enzymes.
An Autophagy Modifier Screen Identifies Small Molecules Capable of Reducing Autophagosome Accumulation in a Model of CLN3-Mediated Neurodegeneration
Authors: Petcherski Anton , Chandrachud Uma , Butz Elisabeth , Klein Madeleine , Zhao Wen-Ning , Reis Surya , Haggarty Stephen , Ruonala Mika , Cotman Susan
Published: November 2019

Alterations in the autophagosomal–lysosomal pathway are a major pathophysiological feature of CLN3 disease, which is the most common form of childhood-onset neurodegeneration. Accumulating autofluorescent lysosomal storage material in CLN3 disease, consisting of dolichols, lipids, biometals, and a protein that normally resides in the mitochondria, subunit c of the mitochondrial ATPase, provides evidence that autophagosomal–lysosomal turnover of cellular components is disrupted upon loss of CLN3 protein function. Using a murine neuronal cell model of the disease, which accurately mimics the major gene defect and the hallmark features of CLN3 disease, we conducted an unbiased search for modifiers of autophagy, extending previous work by further optimizing a GFP-LC3 based assay and performing a high-content screen on a library of ~2000 bioactive compounds. Here we corroborate our earlier screening results and identify expanded, independent sets of autophagy modifiers that increase or decrease the accumulation of autophagosomes in the CLN3 disease cells, highlighting several pathways of interest, including the regulation of calcium signaling, microtubule dynamics, and the mevalonate pathway. Follow-up analysis on fluspirilene, nicardipine, and verapamil, in particular, confirmed activity in reducing GFP-LC3 vesicle burden, while also demonstrating activity in normalizing lysosomal positioning and, for verapamil, in promoting storage material clearance in CLN3 disease neuronal cells. This study demonstrates the potential for cell-based screening studies to identify candidate molecules and pathways for further work to understand CLN3 disease pathogenesis and in drug development efforts.
MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States
Authors: Vasu Srividya , Kumano Kenjiro , Darden Carly M. , Rahman Irum , Lawrence Michael C. , Naziruddin Bashoo
Published: November 2019

Diabetes results from the inability of pancreatic islets to maintain blood glucose concentrations within a normal physiological range. Clinical features are usually not observed until islets begin to fail and irreversible damage has occurred. Diabetes is generally diagnosed based on elevated glucose, which does not distinguish between type 1 and 2 diabetes. Thus, new diagnostic approaches are needed to detect different modes of diabetes before manifestation of disease. During prediabetes (pre-DM), islets undergo stress and release micro (mi) RNAs. Here, we review studies that have measured and tracked miRNAs in the blood for those with recent-onset or longstanding type 1 diabetes, obesity, pre-diabetes, type 2 diabetes, and gestational diabetes. We summarize the findings on miRNA signatures with the potential to stage progression of different modes of diabetes. Advances in identifying selective biomarker signatures may aid in early detection and classification of diabetic conditions and treatments to prevent and reverse diabetes.
Good News for Nuclear Transgene Expression in Chlamydomonas
Authors: Schroda Michael
Published: November 2019

Chlamydomonas reinhardtii is a well-established model system for basic research questions ranging from photosynthesis and organelle biogenesis, to the biology of cilia and basal bodies, to channelrhodopsins and photoreceptors. More recently, Chlamydomonas has also been recognized as a suitable host for the production of high-value chemicals and high-value recombinant proteins. However, basic and applied research have suffered from the inefficient expression of nuclear transgenes. The combined efforts of the Chlamydomonas community over the past decades have provided insights into the mechanisms underlying this phenomenon and have resulted in mutant strains defective in some silencing mechanisms. Moreover, many insights have been gained into the parameters that affect nuclear transgene expression, like promoters, introns, codon usage, or terminators. Here I critically review these insights and try to integrate them into design suggestions for the construction of nuclear transgenes that are to be expressed at high levels.
Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma
Authors: Okada Reona , Koshizuka Keiichi , Yamada Yasutaka , Moriya Shogo , Kikkawa Naoko , Kinoshita Takashi , Hanazawa Toyoyuki , Seki Naohiko
Published: November 2019

To identify novel oncogenic targets in head and neck squamous cell carcinoma (HNSCC), we have analyzed antitumor microRNAs (miRNAs) and their controlled molecular networks in HNSCC cells. Based on our miRNA signature in HNSCC, both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passenger strand) are downregulated in cancer tissues. Moreover, low expression of miR-99a-5p and miR-99a-3p significantly predicts poor prognosis in HNSCC, and these miRNAs regulate cancer cell migration and invasion. We previously showed that passenger strands of miRNAs have antitumor functions. Here, we screened miR-99a-3p-controlled oncogenes involved in HNSCC pathogenesis. Thirty-two genes were identified as miR-99a-3p-regulated genes, and 10 genes (STAMBP, TIMP4, TMEM14C, CANX, SUV420H1, HSP90B1, PDIA3, MTHFD2, BCAT1, and SLC22A15) significantly predicted 5-year overall survival. Notably, among these genes, STAMBP, TIMP4, TMEM14C, CANX, and SUV420H1 were independent prognostic markers of HNSCC by multivariate analyses. We further investigated the oncogenic function of STAMBP in HNSCC cells using knockdown assays. Our data demonstrated that the aggressiveness of phenotypes in HNSCC cells was attenuated by siSTAMBP transfection. Moreover, aberrant STAMBP expression was detected in HNSCC clinical specimens by immunohistochemistry. This strategy may contribute to the clarification of the molecular pathogenesis of this disease.
Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials
Authors: Barreto Sara , Hamel Leonie , Schiatti Teresa , Yang Ying , George Vinoj
Published: November 2019

Cardiac Progenitor Cells (CPCs) show great potential as a cell resource for restoring cardiac function in patients affected by heart disease or heart failure. CPCs are proliferative and committed to cardiac fate, capable of generating cells of all the cardiac lineages. These cells offer a significant shift in paradigm over the use of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes owing to the latter’s inability to recapitulate mature features of a native myocardium, limiting their translational applications. The iPSCs and direct reprogramming of somatic cells have been attempted to produce CPCs and, in this process, a variety of chemical and/or genetic factors have been evaluated for their ability to generate, expand, and maintain CPCs in vitro. However, the precise stoichiometry and spatiotemporal activity of these factors and the genetic interplay during embryonic CPC development remain challenging to reproduce in culture, in terms of efficiency, numbers, and translational potential. Recent advances in biomaterials to mimic the native cardiac microenvironment have shown promise to influence CPC regenerative functions, while being capable of integrating with host tissue. This review highlights recent developments and limitations in the generation and use of CPCs from stem cells, and the trends that influence the direction of research to promote better application of CPCs.
Microwave-Assisted Synthesis of Amikacin Modified N,S co-Doped Carbon Dots for Escherichia coli Detection
Authors: Putri Fajar Amelia Rachmawati , Mudasir Mudasir , Morita Kinichi , Suherman Suherman
Published: November 2019

Fluorescent amikacin modified nitrogen, sulfur co-doped carbon dots (amikacin modified N,S-CDs) were synthesized by a facile and low-cost one-step microwave-assisted specifically for selective detection of Gram-negative bacteria Escherichia coli (E. coli). Amikacin is a semi-synthetic amino glycoside antibiotic and it was employed in this study to increase the fluorescence response of N,S-CDs by providing binding ligand towards E. coli. The effect of thiourea content as the source of nitrogen and sulfur dopants was investigated prior to the preparation of amikacin modified N,S-CDs. The formation of amikacin modified N,S-CDs were characterized by using Fourier transform infrared (FTIR), X-ray diffraction (XRD), Transmission electron microscope (TEM), UV-Vis spectrophotometer, and spectrofluorometer. Amikacin modified N,S-CDs was identified to be successfully synthesized from the wavenumber shift of the C=O stretching mode. Amikacin modified N,S-CDs were amorphous with an average size of 7 nm. Fluorescence spectra showed that the highest intensity was obtained at thiourea content of 50% and amikacin mass of 25 mg. By comparing fluorescence responses of all the investigated amikacin modified N,S-CDs, the limit of detection (LOD) was attained by 25 mg amikacin modified N,S-CDs at 1.526 cfu mL−1.
Investigation of the Lightning Impulse Breakdown Voltage of Mineral Oil based Fe3O4 Nanofluids
Authors: Primo Víctor A. , García Belén , Burgos Juan Carlos , Pérez-Rosa Daniel
Published: November 2019

The recent interest in the development of nanomaterials has led researchers to the study of their electrical properties and the applications that they may have as insulating materials. One of these applications is the use of nanofluids as electrical insulation of power transformers. It has been reported that the dielectric properties of insulating liquids in which small amounts of nanoparticles have been dispersed are, in some cases, superior to those of the base fluids. Although these materials are promising, and their application could lead to advantages for the transformer design and reliability in the future, more research is necessary to evaluate different combination of materials under a wider range of experimental conditions. In this paper, a research on the lightning impulse breakdown voltage of mineral oil and several Fe3O4-based nanofluids is presented. Fluids prepared with different concentrations of nanoparticles were subjected to impulse lightning voltages considering both positive and negative polarities. As shown in this work the positive impulse breakdown voltage of the liquids showed improvements of up to 50%; in the case of the negative impulses not significant improvements were obtained.
Effect of Noncovalent Dispersion of Poly(Ethylene Oxide) in Columnar Polyether-Based Discotic Liquid Crystal on the Ionic Conductivity and Dynamics of Lithium Ions
Authors: Hwang Jih-Dar , Chen Po-Ying , Ding Shang-Wu , Ong Chi Wi
Published: November 2019

The ionic conductivity of an electrolyte is represented by a product of carrier density, charge (electric), and ionic mobility. The overall goal of this study was to provide an insight into the influence of lithium ion conductivity and dynamic when a continuous discotic liquid crystal (DLC) matrix of hexaazatrinapthylene-polyether, HATN-TEG-1, is doped with a small amount of polyethylene oxide (PEO, 5% of MW 8000). The favorable non-covalent interactions between PEO and the DLC triethylene glycol side-chains is supported by the maintenance of the mesophase. The lithium ionic conductivity of HATN-TEG-1 was found to be 1.1 × 10−6 S cm−1, which is better than the corresponding HATN-TEG-1-5%PEO-8000 with a value of 6.06 × 10−7 S cm−1. These results are further supported by the dynamics of the lithium ions in HATN-TEG-1 and HATN-TEG-1-5%PEO-8000 as characterized by 7Li, and 1H NMR spin-lattice relaxation time and self-diffusion coefficient measurements. Though the additional PEO was found to increase the ion carriers, the significant lowering of the ionic conductivity may be attributed to the more pronounced decrease of the mobility of the ionic part when the HATN-TEG-1 matrix is dispersed with PEO. This finding indicates that the doping of 5% PEO onto the matrix of HATN-TEG-1 DLC has an adverse effect on both its diffusion rate and ion conductivity.
Tunable and Polarization-Independent Plasmon-Induced Transparency in a Fourfold Symmetric Metal-Graphene Terahertz Metamaterial
Authors: Wang Guanqi , Zhang Xianbin , Wei Xuyan , Zhang Gaoqi
Published: November 2019

The introduction of graphene into metamaterials allows for more flexible and convenient control of electromagnetic waves. In this paper, one simple plasmon-induced transparency (PIT) structure with tunability and polarization independence is investigated in the terahertz (THz) regime. The simulation results indicate that the transparent window can be manipulated in a wide range and even switched off by merely changing the Fermi energy of graphene. By continuously altering the resonance intensity of the dark resonator using the graphene, the PIT resonance can be actively manipulated. The behavior can be elucidated by the classical coupled two-particle model, which corresponds well to the simulation results. Owing to the fourfold symmetric structure, the proposed PIT device exhibits polarization-independent characteristics. This work provides design guidance for metal-graphene THz modulators.
First Record of Amphioxus Branchiostoma californiense (Amphioxiformes: Branchiostomatidae) Adjacent to a Shallow Submarine Hydrothermal System at Banderas Bay (Mexico)
Authors: Rodríguez-Uribe María Carolina , Chávez-Dagostino Rosa María , Del Moral-Flores Luis Fernando , Bravo-Olivas Myrna Leticia
Published: November 2019

Shallow submarine hydrothermal vent systems assume differentiated environmental conditions. Some specimens of Branchiostoma californiense were found in the sediments of the influence area of the shallow hydrothermal venting in Punta Mita. This is the only lancelet species registered for the Mexican Pacific. The meristic and morphometric characteristics of the organisms first collected in unconsolidated sediments of this shallow system were reviewed, in order to determine the species. We confirm that it is the same species. This represents the first record of it for both the Banderas bay and in the influence area of a shallow hydrothermal system.