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The "dual carbon" goal has made it a mainstream trend for new energy stations (NESs) and energy storage stations (ESSs) to jointly participate in market regulation. This paper proposes a multiple time scale distributed optimization method for NESs and ESSs based on the alternate direction multiplier method (ADMM). By first considering the uncertainty of new energy output and the volatility of electricity market prices, a multi time scale revenue model is constructed for day-ahead, intraday, and real-time markets. Then, the objective function is built by maximizing the comprehensive market revenues and is simplified using the synergistic effect of NESs and ESSs. Next, the simplified objective function is solved by the ADMM, and the revenues are maximized while each energy meets the relevant constraints. Lastly, the 33-node network topology is used to illustrate the feasibility of the proposed method. The simulation results show that after optimization, the output of NESs and ESSs can coordinate work in day-ahead, intraday, and real-time markets, while the abandonment power of wind and light is significantly improved. [ABSTRACT FROM AUTHOR]

Melanoma is the most severe type of skin cancer and among the most malignant neoplasms in humans. With the growing incidence of melanoma, increased numbers of therapeutic options, and the potential to target specific proteins, understanding the basic mechanisms underlying the disease's progression and resistance to treatment has never been more important. LOXL3, SNAI1, and NES are key factors in melanoma genesis, regulating tumor growth, metastasis, and cellular differentiation. In our study, we explored the potential role of LOXL3, SNAI1, and NES in melanoma progression and metastasis among patients with dysplastic nevi, melanoma in situ, and BRAF+ and BRAF− metastatic melanoma, using immunofluorescence and qPCR analysis. Our results reveal a significant increase in LOXL3 expression and the highest NES expression in BRAF+ melanoma compared to BRAF−, dysplastic nevi, and melanoma in situ. As for SNAI1, the highest expression was observed in the metastatic melanoma group, without significant differences among groups. We found co-expression of LOXL3 and SNAI1 in the perinuclear area of all investigated subgroups and NES and SNAI1 co-expression in melanoma cells. These findings suggest a codependence or collaboration between these markers in melanoma EMT, suggesting new potential therapeutic interventions to block the EMT cascade that could significantly affect survival in many melanoma patients. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the suppression effect of a nonlinear energy sink (NES) on the wind-vortex-induced pipe vibration and explore the influence of damping, stiffness, and NES installation position on the suppression effect. In this work, the wind-vortex-induced vibration of an elastic pipe of a deepwater jacket was studied, and vibrations were suppressed by using an NES. A van der Pol wake oscillator was used to simulate vortex-induced force, and the dynamic equation of the pipe considering the NES was established. The Galerkin method was applied to discretize the motion equation, and the vortex-induced vibration (VIV) of the pipe at reduced wind speeds was numerically analyzed. The novelty of this research is that particle swarm optimization was used to optimize the parameters of the NES to improve vibration suppression. The influence of the installation position, nonlinear stiffness, and damping parameters of the NES on vibration suppression was analyzed. Results showed that the optimized parameter combinations of the NES can effectively reduce wind-vortex-induced pipe vibration. The installation position of the NES had a significant effect on vibration suppression, and the midpoint of the pipe was the optimal NES installation position. An increase in stiffness or a 10% decrease in damping may cause vibration suppression failure. The results of this study provide some guidance for VIV suppression in deepwater jacket pipes. [ABSTRACT FROM AUTHOR]

Non-equilibrium processes in the atmosphere and water were described in this paper. Spectral analysis by NES and DNES methods was applied to research water structure. The energy spectrum of water is obtained due to the non-equilibrium process of evaporation of water drops. The term Non-equilibrium energy spectrum (NES) is used in this method. The distribution function according to hydrogen bond energies f(E) is measured in reciprocal electron volts (eV-1). The differential energy spectrum DNES represents the difference between the investigated sample's NES and the control sample's NES. It is assumed that the combined influence of all factors other than those under study is identical for the control and sample. The effects of gas-solid heat exchange and calcium carbonate (CaCO3) decomposition were described. Our research aims to show peaks at 713 and in the 873 - 879 cm-1 due to shared environmental influences on calcium carbonate. The purpose of the article is to demonstrate that by studying the spectral parameters at 713 and in the range of 873 ÷ 879 cm-1, an assessment can be made for the application of the impact of water with different physicochemical parameters, air humidity, thermal effects on the quality of lime mortar solutions and chemical processes with carbon dioxide (CO2). [ABSTRACT FROM AUTHOR]

The system of linear oscillators coupled to multi-degree-of-freedom (MDOF) nonlinear attachment with combined periodic and stochastic seismic excitation is studied in this paper. The MDOF nonlinear attachment passively absorbs broadband energy from the linear system in a unidirectional and irreversible way numerically, which acts as a nonlinear energy sink (NES) in essence. The typical cubic nonlinear terms and sinusoidal nonlinear terms are considered, respectively. The periodic generalized harmonic wavelet (PGHW) and wavelet-Galerkin methods are used for motion equations, then a set of nonlinear algebraic equations can be obtained to get the wavelet coefficient of response. The quasi-Newton method is selected to solve these equations, which is more effective than the Newton method. In the numerical example, the algorithms of Single rank inverse Broyden (Rank-1 iB), Rank-2 Broyden–Fletcher–Shanno (Rank-2 BFS), Davidon–Fletcher–Powell (DFP), and Broyden–Fletcher–Goldfarb–Shanno (BFGS) are used to estimate the Jacobian matrix. The number of iterations, calculation time, and relative error are listed and compared, and it is concluded that the algorithm of Rank-1 iB is a better one for solving this problem in both cases. Finally, the displacement and estimated power spectral density (EPSD) of the response are obtained and shown. [ABSTRACT FROM AUTHOR]

Background: With the fast development of aerospace technology, in order to improve the carrying efficiency of spacecraft, its design is gradually moving towards lighter weight and large size, such as solar wings, satellite antennas, and space manipulators. However, the application of flexible appendage can easily arouse obvious vibration during mission, which affects the operation accuracy and even threaten the safety of spacecraft structure. Purpose: To improve the working accuracy of spacecraft, the passive control strategy is adopted to suppress the serious vibration of the flexible appendage under different loads. Methods: Based on the absolute nodal coordinate formulation (ANCF), the dynamic model of spacecraft flexible appendage is established. Firstly, the single-degree-offreedom (1-DOF) and two-degree-of-freedom (2-DOF) NES are applied to the flexible beam structure. On this basis, the vibration characteristics and dynamic evolution of the coupled system are investigated under different load conditions. Results: When the initial amplitude of the NES is larger, the vibration reduction efficiency of the system becomes higher. At the same time, increasing the additional mass of the NES could also improve the effect of the structural vibration suppression. Conclusion: Vibration suppression effects on the dynamic characteristics of flexible appendage are closely related to the installation position of nonlinear energy sink. Compared with the 1-DOF NES, the 2-DOF NES has a better energy suppression effect, and the vibration energy transfer rate from the main system to the subsystem is more obvious when the additional total mass is the same. [ABSTRACT FROM AUTHOR]

Appropriate nucleo-cytoplasmic partitioning of proteins is a vital regulatory mechanism in phytohormone signaling and plant development. However, how this is achieved remains incompletely understood. The Karyopherin (KAP) superfamily is critical for separating the biological processes in the nucleus from those in the cytoplasm. The KAP superfamily is divided into Importin α (IMPα) and Importin β (IMPβ) families and includes the core components in mediating nucleocytoplasmic transport. Recent reports suggest the KAPs play crucial regulatory roles in Arabidopsis development and stress response by regulating the nucleo-cytoplasmic transport of members in hormone signaling. However, the KAP members and their associated molecular mechanisms are still poorly understood in maize. Therefore, we first identified seven IMPα and twenty-seven IMPβ genes in the maize genome and described their evolution traits and the recognition rules for substrates with nuclear localization signals (NLSs) or nuclear export signals (NESs) in plants. Next, we searched for the protein interaction partners of the ZmKAPs and selected the ones with Arabidopsis orthologs functioning in auxin biosynthesis, transport, and signaling to predict their potential function. Finally, we found that several ZmKAPs share similar expression patterns with their interacting proteins, implying their function in root development. Overall, this article focuses on the Karyopherin superfamily in maize and starts with this entry point by systematically comprehending the KAP-mediated nucleo-cytoplasmic transport process in plants, and then predicts the function of the ZmKAPs during maize development, with a perspective on a closely associated regulatory mechanism between the nucleo-cytoplasmic transport and the phytohormone network. [ABSTRACT FROM AUTHOR]

Gesneriaceae plant family is comprised of resurrection species, namely Boea hygrometrica and Paraboea rufescens, that are native to the Southeast Asia and Haberlea rhodopensis, Ramonda myconi, and Ramonda serbica, which are mainly found in the Balkan Peninsula. Haberlea rhodopensis is known to be able to survive extreme and prolonged dehydration. Study was carried out after the dried plant Haberlea rhodopensis Friv. had been hydrated and had reached its fresh state. Two juice samples were collected from the plant blossom: The first sample was prepared with 1% filtered water through a patented EVOdrop device. Then the sample was saturated with hydrogen with EVOdrop booster to a concentration of 1.2 ppm, pH = 7.3, ORP = −390 mV. This first sample was prepared with filtered tap water from Sofia, Bulgaria. The second sample, which was a control one, was developed with tap water from Sofia, Bulgaria, consisting of 1% solutions of Haberlea rhodopensis. A study revealed that during the drying process in H. rhodopensis the number of free water molecules decreases, and water dimers are formed. The aim of our study was to determine the number of water molecules in clusters in 1% solutions of hydrated H. rhodopensis plants. Results were analyzed according to the two types of water used in the experiment. Th EVOdrop device is equipped with an ultranano membrane and rotating jet nozzle to create a vortex water and saturation thanks to a second device EVObooster to obtain hydrogen-rich water. In the current study Hydrogen-rich water is referred to as Hydrogen EVOdrop Water (HEW). Research was conducted using the following methods—spectral methods non-equilibrium energy spectrum (NES) and differential non-equilibrium energy spectrum (DNES), mathematical models, and study of the distribution of water molecules in water clusters. In a licensed Eurotest Laboratory, the research of tap water before and after flowing through the EVOdrop device was proven. Studies have been carried out on the structuring of water molecule clusters after change of hydrogen bond energies. The restructuring comes with rearrangement of water molecules by the energy levels of hydrogen bonds. Local extrema can be observed in the spectrum with largest amount of water molecules. The structural changes were tested using the NES and DNES spectral methods. The conducted research proved that the application of EVOdrop device and EVObooster changes the parameters of water to benefit hydration and health. [ABSTRACT FROM AUTHOR]

The generation of astrocytes from human induced pluripotent stem cells has been hampered by either prolonged differentiation—spanning over two months—or by shorter protocols that generate immature astrocytes, devoid of salient mature astrocytic traits pivotal for central nervous system (CNS) modeling. We directed stable hiPSC-derived neuroepithelial stem cells to human iPSC-derived Astrocytes (hiAstrocytes) with a high percentage of star-shaped cells by orchestrating an astrocytic-tuned culturing environment in 28 days. We employed RT-qPCR and ICC to validate the astrocytic commitment of the neuroepithelial stem cells. To evaluate the inflammatory phenotype, we challenged the hiAstrocytes with the pro-inflammatory cytokine IL-1β (interleukin 1 beta) and quantitatively assessed the secretion profile of astrocyte-associated cytokines and the expression of intercellular adhesion molecule 1 (ICAM-1). Finally, we quantitatively assessed the capacity of hiAstrocytes to synthesize and export the antioxidant glutathione. In under 28 days, the generated cells express canonical and mature astrocytic markers, denoted by the expression of GFAP, AQP4 and ALDH1L1. In addition, the notion of a mature phenotype is reinforced by the expression of both astrocytic glutamate transporters EAAT1 and EAAT2. Thus, hiAstrocytes have a mature phenotype that encompasses traits critical in CNS modeling, including glutathione synthesis and secretion, upregulation of ICAM-1 and a cytokine secretion profile on a par with human fetal astrocytes. This protocol generates a multifaceted astrocytic model suitable for in vitro CNS disease modeling and personalized medicine. [ABSTRACT FROM AUTHOR]

The NES (nonlinear energy sink) is a new type of nonlinear tuned mass damper that is connected to the shock-absorbing main structure through strong nonlinear stiffness and viscous damping. The vibrational energy in the main structure is transferred to the NES oscillator by means of target energy transfer. A shaking table test of a 1:4 scaled RC (Reinforced Concrete) frame structure model with a new type of NES shock absorber was conducted to study the damping effect of the NES shock absorber, especially for the influence of joint strength and deformation. The NES used in this experiment has a relatively large nonlinear stiffness and a wide vibration absorption frequency band. The variation of reinforcement strains, node failure mode, and structural natural frequency of 1 story and two-layer joints of the model frame structure with NES were studied. The test results showed that NES could effectively reduce the strains of longitudinal reinforcement and stirrup in beams and columns and delay the plastic hinge development at the bottom and the top of the column. The frame model with NES installed has failures at the beam ends and shear failures at the nodes, realizing the seismic mechanism of solid columns and weak beams. Compared with ordinary seismic structures, the NES can effectively reduce the shear stress of concrete at the joints and alleviate the shear failure of joints. The final failure of the NES shock absorbing structure was the yielding of the steel bars at the bottom of the column and the crushing of the concrete at the foot of the column, and the connection between the column foot and the backplane became loose simultaneously. The decreasing rate of the vibration frequency declined due to the NES with varied broadband absorbing capability. It can be seen that the NES shock absorber not only has a good effect on reducing the seismic response of the structure, but more importantly, the damage of the structural nodes is greatly reduced, and therefore, the seismic capacity of the structure improved. [ABSTRACT FROM AUTHOR]

The aim of this paper is to investigate the vibration suppression effect of a nonlinear energy sink (NES) on the wind-vortex-induced vibration of deep-water jacket pipes. Based on nonlinear dynamical theories, the coupled dynamic equation of a deep-water jacket pipe with NES was established, and the nonlinear response characteristics and motion stability of the system were studied by using the multi-scale mixed harmonic balance method and Routh–Hurwitz criterion. The paper also analyzed the influence of the nonlinear stiffness and damping parameters of an NES on the dynamic response of the pipe. It is concluded that when the nonlinear stiffness of an NES increases to a certain extent, the motion response of the pipe appeared as a saddle-node and Hopf bifurcation, and the vibration amplitude of the pipe is greatly suppressed. For a system with nonlinear motion, NES damping mainly affects the range of the unstable region. For the system without nonlinear motion, the increases in NES damping will reduce the amplitude near the resonance region. Selecting proper parameters of an NES nonlinear stiffness and damping can effectively suppress the vortex-induced vibration of pipes. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV), the pathogen of several human malignancies, encodes many proteins required to be transported into the nucleus for viral DNA reproduction and nucleocapsids assembly in the lytic replication cycle. Here, fluorescence microscope, mutation analysis, interspecies heterokaryon assays, co-immunoprecipitation assay, RNA interference, and Western blot were performed to explore the nuclear import mechanism of EBV encoded BLLF2 protein. BLLF2 was shown to be a nucleocytoplasmic shuttling protein neither by a chromosomal region maintenance 1 (CRM1)- nor by a transporter associated with antigen processing (TAP)-dependent pathway. Yet, BLLF2's two functional nuclear localization signals (NLSs), NLS1 (16KRQALETVPHPQNRGR31) and NLS2 (44RRPRPPVAKRRRFPR58), were identified, whereas the predicted NES was nonfunctional. Finally, BLLF2 was proven to transport into the nucleus via a Ran-dependent and importin β1-dependent pathway. This mechanism may contribute to a more extensive insight into the assembly and synthesis of EBV virions in the nucleus, thus affording a new direction for the treatment of viruses. [ABSTRACT FROM AUTHOR]

Chromosome region maintenance 1 (CRM1) exports nuclear export signal (NES) containing cargos from nucleus to cytoplasm and plays critical roles in cancer and viral infections. Biochemical and biophysical studies on this protein were often obstructed by its low purification yield and stability. With the help of PROSS server and NES protection strategy, we successfully designed three small fragments of CRM1, each made of four HEAT repeats and capable of binding to NESs in the absence of RanGTP. One of the fragments, C7, showed dramatically improved purification yield, thermostability, mechanostability, and resistance to protease digestion. We showed by isothermal titration that the protein kinase inhibitor NES binds to C7 at 1.18 μM affinity. Direct binding to C7 by several reported CRM1 inhibitors derived from plants were verified using pull‐down assays. These fragments might be useful for the development of CRM1 inhibitors towards treatment of related diseases. The strategy applied here might help to tackle similar problems encountered in different fields. [ABSTRACT FROM AUTHOR]

Replication protein A (RPA), a heterotrimeric complex, is the major single‐stranded DNA binding protein in eukaryotes. Recently, we characterized RPA from Trypanosoma cruzi, showing that it is involved in DNA replication and DNA damage response in this organism. Better efficiency in differentiation from epimastigote to metacyclic trypomastigote forms was observed in TcRPA‐2 subunit heterozygous knockout cells, suggesting that RPA is involved in this process. Here, we show that RPA cellular localization changes during the T. cruzi life cycle, with RPA being detected only in the cytoplasm of the metacyclic and bloodstream trypomastigotes. We also identify a nuclear export signal (NES) in the trypanosomatid RPA‐2 subunit. Mutations in the negatively charged residues of RPA‐2 NES impair the differentiation process, suggesting that RPA exportation affects parasite differentiation into infective forms. [ABSTRACT FROM AUTHOR]

Current study was aimed to evaluate the relationship between emotional eating and night eating syndrome (NES) with sleep quality among adolescents in Tabriz-Iran. The current study was conducted among eighty adolescent boys aged 12–16 years old from Tabriz-Iran. Night eating syndrome and Emotional eating were measured by validated specific questionnaires. Pittsburgh Sleep Quality Index questionnaire (PSQI) was used for assessment of sleep quality. Emotional and very emotional eaters had significantly higher protein and fat intake. Among components of PSQI, subjective sleep quality, sleep disturbances and daytime dysfunction scores among emotional and very emotional eaters were significantly higher. Moreover, adolescents with NES, had higher PSQI score and lower carbohydrate intake; whereas, intake of fat among NES group was significantly higher (P < 0.05). Our results indicated poor sleep quality and higher dietary fat intake among adolescents with emotional eating disorder and NES. Therefore, it is necessary to consider healthy nutritional pattern including low fat intake in prevention of developing emotional eating and NES among adolescents. [ABSTRACT FROM AUTHOR]

Copyright of Applied Mathematics & Mechanics (1000-0887) is the property of Applied Mathematics & Mechanics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Night Eating Syndrome (NES) refers to an abnormal eating behavior which presents as evening hyperphagia consuming >25% calorie intake and/or nocturnal awaking with food ingestion which occurs ≥2 times per week. Although the syndrome has been described more than seven decades ago, the literature has been growing slowly on its etiology, diagnosis, and treatment. Areas covered: The proposed treatment options for NES are all at a case-study level. Moreover, our understanding of its etiology, comorbidities, and diagnosis is still premature. We performed a literature review in Medline/PubMed to identify all the studies proposing a management plan for NES and summarized all the existing data on its diagnosis and treatment. Expert opinion: To date, none of the proposed treatment options for NES have been promising and long-term data on its efficacy is lacking. The slow growth of evidence on this debilitating but underreported condition may be due to unawareness among clinicians, under-reporting by patients, and unrecognized diagnostic criteria. Objective screening of symptoms during office visits especially for patients at a high-risk for NES will identify more patients suffering from the syndrome. [ABSTRACT FROM AUTHOR]

Fennel (Foeniculum vulgare Mill.) is a member of family Apiaceae. Trans-anethole, the major component of Fennel essential oil (FEO), possesses antioxidant and hepatoprotective effects. Transdermal nanoemulsions (NEs) are advanced colloidal systems for systemic and controlled drug delivery through the stratum corneum barrier. FEO NEs were prepared using the oil Lauroglycol™ 90, as it provides a larger NE existence zone than Captex® 300, in the constructed phase diagrams. Six systems were prepared using Tween20/propylene glycol (S/CoS) in the ratios 2:1 and 3:1 with oil to S/CoS mass ratios 1:9, 2:8 and 3:7. Physicochemical characterization revealed optimum properties regarding thermodynamic stability, droplet size and pH with a Newtonian flow pattern. In vitro permeation study in rat skin revealed the highest cumulative amount permeated (µg/cm2), flux and permeability coefficient values for F4 made up of 2% FEO, 4.67% Lauroglycol™ 90, 60% S/CoS in the ratio 3:1. Results of the in vivo hepatic dysfunction study in rats indicate promising significant amelioration of liver function reflected in ALT, AST, ALP, bilirubin, albumin, malondialdehyde and ammonia plasma levels. The results signify the promising approach of FEO NEs in achieving remedy of liver toxicity. The most promising effect is inherent to F4 which imparts a more positive effect than FEO. [ABSTRACT FROM AUTHOR]

Copyright of Applied Mathematics & Mechanics (1000-0887) is the property of Applied Mathematics & Mechanics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Shc family signalling adaptors connect activated transmembrane receptors to proximal effectors, and most also contain a sequence involved in clathrin-mediated receptor endocytosis. Notably, this AP2 adaptin-binding motif (AD) is absent from the ShcD (also known as Shc4) homolog, which also uniquely promotes ligand-independent phosphorylation of the epidermal growth factor receptor (EGFR). We now report that cultured cells expressing ShcD exhibit reduced EGF uptake, commensurate with a decrease in EGFR surface presentation. Under basal conditions, ShcD colocalises with the EGFR and facilitates its phosphorylation, ubiquitylation and accumulation in juxtanuclear vesicles identified as Rab11-positive endocytic recycling compartments. Accordingly, ShcD also functions as a constitutive binding partner for the E3 ubiquitin ligase Cbl. EGFR phosphorylation and focal accumulation likewise occur upon ShcD co-expression in U87 glioma cells. Loss of ShcD phosphotyrosine-binding function or insertion of the ShcA AD sequence each restore ligand acquisition through distinct mechanisms. The AD region also contains a nuclear export signal, indicating its multifunctionality. Overall, ShcD appears to possess several molecular permutations that actively govern the EGFR, which may have implications in development and disease. [ABSTRACT FROM AUTHOR]

The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end. [ABSTRACT FROM AUTHOR]

China's total floating population exceeded 245 million at the end of 2013 and is the largest mobile population in the world. This paper explores the spatial distribution pattern and change characteristics of the net floating population at county scale from 2000 to 2010 using census data. The results show the following: (1) the net floating population increased by 120 million over 10 years, and the mobility of the population had enhanced in this period; (2) the floating population migrated to the three economic zones and provincial capital cities, while the traditional agricultural regions with dense populations experienced continuous outflow of population (which altered spatial agglomeration patterns); (3) eastern China has a high level of natural environment suitability and was a major destination area, but more pressures were placed on the carrying capacity of big cities; and (4) western China, with a relatively weak carrying capacity for resources and environment, was a net outflow region in 2010 - although five provinces had small-scale net inflow because of western-style development strategies. This study is offered as a contribution to understanding the features of China's floating population and will be useful for those shaping policies that guide population migration. [ABSTRACT FROM AUTHOR]

In this work, we analyse the characteristics of the entrepreneurial environment and examine whether a relation exists between these characteristics and the country's stage of economic development. For this purpose, we use the national experts' opinions from the Global Entrepreneurship Monitor Project. We aim to identify whether the experts' opinions are in line with the different stages of economic development, or more specifically, whether we can see patterns in their opinions that reflect the different stages in the entrepreneurial environment of countries. If this proves to be the case, the information provided by the national experts in terms of facilitators of, and obstacles to, entrepreneurship and their recommendations for boosting entrepreneurial activity, would be useful to national governments in the design of entrepreneurial policies to help the country to move up to a higher stage of economic development. We use data from the survey of 1259 GEM project national experts from the 67 countries that participated in 2013. Our results confirm the existence of patterns that could be useful for policymakers dealing with entrepreneurship. [ABSTRACT FROM AUTHOR]

The in vitro isolation, identification, differentiation, and neurogenesis characterization of the sources of mesenchymal stem cells (MSCs) were investigated to produce two types of cells in culture: neural cells and neural stem cells (NSCs). These types of stem cells were used as successful sources for the further treatment of central nervous system defects and injuries. The mouse bone marrow MSCs were used as the source of the stem cells in this study. β-Mercaptoethanol (BME) was used as the main inducer of the neurogenesis pathway to induce neural cells and to identify NSCs. Three types of neural markers were used: nestin as the immaturation stage marker, neurofilament light chain as the early neural marker, and microtubule-associated protein 2 as the maturation marker through different time intervals in the neurogenesis process starting from the MSCs, (as undifferentiated cells), NSCs, production stages, and toward neuron cells (as differentiated cells). The results of different exposure times to BME of the neural markers analysis done by immunocytochemistry and real time-polymerase chain reaction helped us to identify the exact timing for the neural stemness state. The results showed that the best exposure time that may be used for the production of NSCs was 6 hours. The best maintenance media for NSCs were also identified. Furthermore, we optimized exposure to BME with different times and concentrations, which could be an interesting way to modulate specific neuronal differentiation and obtain autologous neuronal phenotypes. This study was able to characterize NSCs in culture under differentiation for neurogenesis in the pathway of the neural differentiation process by studying the expressed neural genes and the ability to maintain these NSCs in culture for further differentiation in thousands of functional neurons for the treatment of brain and spinal cord injuries and defects. [ABSTRACT FROM AUTHOR]

Copyright of Biochemistry & Cell Biology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Vibratory energy exchanges between two coupled oscillators is studied: the main elasto-plastic oscillator is coupled to a nonlinear energy sink(NES) with nonsmooth potential. Both oscillators are under pre-stressing terms. Two different methods are implemented for tracing system behaviours: (i) the time-event-driven technique which builds exact solutions of governing equations of the system phase by phase and (ii) the multi-scale method which traces system behaviours at different scales of time. It detects invariant of the system at fast timescale and equilibrium/singular points at slow timescales. The pre-stressing terms produce a more complex shape for the invariant, while detected dynamics at slow timescale let us have control at the behaviour of the system during its quasi-steady-state regime(s) which leads to have analytical design tools for tuning parameters of nonlinear energy sink according to design purposes (passive control and/or energy harvesting). [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the interference of nucleocytoplasmic trafficking with the establishment and maintenance of various cancers. Nucleocytoplasmic transport is highly regulated and coordinated, involving different nuclear transport factors or receptors, importins and exportins, that mediate cargo transport from the cytoplasm into the nucleus or the other way round, respectively. The exportin CRM1 (Chromosome region maintenance 1) exports a plethora of different protein cargoes and ribonucleoprotein complexes. Structural and biochemical analyses have enabled the deduction of individual steps of the CRM1 transport cycle. In addition, CRM1 turned out to be a valid target for anticancer drugs as it exports numerous proto-oncoproteins and tumor suppressors. Clearly, detailed understanding of the flexibility, regulatory features and cooperative binding properties of CRM1 for Ran and cargo is a prerequisite for the design of highly effective drugs. The first compound found to inhibit CRM1-dependent nuclear export was the natural drug Leptomycin B (LMB), which blocks export by competitively interacting with a highly conserved cleft on CRM1 required for nuclear export signal recognition. Clinical studies revealed serious side effects of LMB, leading to a search for alternative natural and synthetic drugs and hence a multitude of novel therapeutics. The present review examines recent progress in understanding the binding mode of natural and synthetic compounds and their inhibitory effects. [ABSTRACT FROM AUTHOR]

Targeted energy transfer between a main oscillator with a set of parallel Saint-Venant elements and a nonlinear energy sink with a general nonlinear and odd potential function around 1:1 resonance is studied. The complexified system has been investigated at fast and slow time scales by detecting its invariant manifold, equilibrium and singular points, which can explain bifurcation(s) and different regimes of the system. Then, we introduce an example which treats vibratory energy exchanges between a main oscillator with two parallel Saint-Venant elements and a coupled cubic nonlinear energy sink. Finally, analytical predictions are compared with results obtained by numerical integrations of system equations. [ABSTRACT FROM AUTHOR]

We try to enlighten the time multi-scale energy exchange between a main oscillator of Bouc-Wen type and a nonlinear energy sink. A general methodology is presented to detect the invariant manifold of the system at fast time scale and then to search equilibrium points and fold singularities at the slow time scale. A numerical example is enclosed to show the application of the coupled nonlinear energy sink in passive control of Bouc-Wen type main structures. [ABSTRACT FROM AUTHOR]

Background: The influenza A virus NS1 protein is a virulence factor and an antagonist of host cell innate immune responses. During virus infection NS1 protein has several functions both in the nucleus and in the cytoplasm and its intracellular localization is regulated by one or two nuclear localization signals (NLS) and a nuclear export signal (NES). Methods: In order to investigate the role of NS1 NES in intracellular localization, virus life cycle and host interferon responses, we generated recombinant A/Udorn/72 viruses harboring point mutations in the NES sequence. Results: NS1 NES was found to be inactivated by several of the mutations resulting in nuclear retention of NS1 at late stages of infection confirming that this sequence is a bona fide functional NES. Some of the mutant viruses showed reduced growth properties in cell culture, inability to antagonize host cell interferon production and increased p-IRF3 levels, but no clear correlation between these phenotypes and NS1 localization could be made. Impaired activation of Akt phosphorylation by the replication-deficient viruses indicates possible disruption of NS1-p85β interaction by mutations in the NES region. Conclusion: We conclude that mutations within the NS1 NES result in impairment of several NS1 functions which extends further from the NES site being only involved in regulating the nuclear-cytoplasmic trafficking of NS1. [ABSTRACT FROM AUTHOR]

Multi-scale dynamics of two coupled oscillators, the linear one with varying mass and a non-smooth light system is studied. The light system, namely nonlinear energy sink (NES) is implemented for passively controlling the linear system against external impulses and/or forces. Obtained invariant manifold of the system at fast time scale let us explain the system behavior during its transient and steady-state regime while predicted dynamics of the system at slow time scale let us detect the positions of fixed and fold singularities by explanation of its behavior. [ABSTRACT FROM AUTHOR]

Inhibitory Per/Arnt/Sim (PAS) domain protein (IPAS) is a splice variant of hypoxia-inducible factor (HIF)-3α, and possesses two entirely different functions. One is as a transcriptional repressor against HIF-dependent hypoxic gene activation. The other is as a pro-apoptotic factor by direct binding to the pro-survival protein Bcl-xL and its related proteins on mitochondria. Presently, the regulatory mechanism that determines the intracellular distribution of IPAS to fulfill each of the two functions is unknown. As a first step towards elucidation of the mechanism, nucleocytoplasmic transport signals of IPAS were explored. A bipartite-like nuclear localization signal (NLS) was found in the N-terminal region by the deletion and mutation analysis of EGFP-IPAS. In addition, the helix-loop-helix domain showed weak nuclear import/retention activity. A leptomycin B-sensitive nuclear export signal (NES) was localized in the C-terminal region of the protein. A proline-rich region supported the NES activity. These NLS and NES are not carried by the other variants of HIF-3α due to differential exon usage. These results strongly suggest that IPAS is a nucleocytoplasmic shuttling protein. [ABSTRACT FROM AUTHOR]

Nuclear import and export of viral RNA and proteins are critical to the replication cycle of viruses that replicate in the nucleus. Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the order Mononegavirales. BDV has several distinguishing features, one of the most striking being the site of its replication. BDV RNA is transcribed and replicated in the nucleus, while most other negative-strand RNA viruses replicate in the cytoplasm. Therefore, the nucleocytoplasmic trafficking of BDV macromolecules plays a key role in virus replication. Growing evidence indicates that several BDV proteins, including the nucleoprotein, phosphoprotein, protein X and large protein, contribute to the nucleocytoplasmic trafficking of BDV ribonucleoprotein (RNP). The directional control of BDV RNP trafficking is likely determined by the ratios of and interactions between the nuclear localization signals and nuclear export signals in the RNP. In this review, we present a comprehensive view of several unique mechanisms that BDV has developed to control its RNP trafficking and discuss the significance of BDV RNP trafficking in the replication cycle of BDV. [ABSTRACT FROM AUTHOR]

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Influenza A virus NS1 protein has developed two main IFN-antagonizing mechanisms by inhibiting retinoic-acid-inducible gene I (RIG-I) signal transduction, or by suppressing cellular pre-mRNA processing through binding to cleavage and polyadenylation specific factor 30 (CPSF30). However, the precise effects of NS1 on suppressing type I IFN induction have not been well characterized. Here we report that compared with PR/8/34 NS1, which is localized partially in the cytoplasm and has strong IFN-antagonizing ability via specifically inhibiting IFN-β promoter activity, H5N1 NS1 has strikingly different characteristics. It mainly accumulates in the nucleus of transfected cells and exerts rather weak IFN-counteracting ability through suppression of the overall gene expression. The M101I mutation of H5N1 NS1, namely H5-M101I, fully reversed its functions. H5-M101I gained the ability to specifically inhibit IFN-β promoter activity, translocate to the cytoplasm, and release CPSF30. The previously reported NES (nuclear export signal) (residues 138-147) was unable to lead H5N1 NS1 to translocate. This suggests that other residues may serve as a potent NES. Findings indicated that together with leucine-100, methionine-101 enhanced the regional NES. In addition, methionine-101 was the key residue for the NS1-CPSF30 interaction. This study reveals the importance of methionine-101 in the influenza A virus life cycle and may provide valuable information for antiviral strategies. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factors (HIFs) regulate more than 200 genes involved in cellular adaptation to reduced oxygen availability. HIFs are heterodimeric transcription factors that consist of one of three HIF-α subunits and a HIF-β subunit. Under normoxic conditions the HIFα subunit is hydroxylated by members of a family of prolyl-4-hydroxylase domain (PHD) proteins, PHD1, PHD2 and PHD3, resulting in recognition by von-Hippel-Lindau protein, ubiquitylation and proteasomal degradation. It has been suggested that PHD2 is the key regulator of HIF-1α stability in vivo. Previous studies on the intracellular distribution of PHD2 have provided evidence for a predominant cytoplasmic localisation but also nuclear activity of PHD2. Here, we investigated functional nuclear transport signals in PHD2 and identified amino acids 196-205 as having a crucial role in nuclear import, whereas amino acids 6-20 are important for nuclear export. Fluorescence resonance energy transfer (FRET) showed that an interaction between PHD2 and HIF-1α occurs in both the nuclear and cytoplasmic compartments. However, a PHD2 mutant that is restricted to the cytoplasm does not interact with HIF-1α and shows less prolyl hydroxylase activity for its target HIF-1α than wild-type PHD2 located in the nucleus. Here, we present a new model by which PHD2-mediated hydroxylation of HIF-1α predominantly occurs in the cell nucleus and is dependent on very dynamic subcellular trafficking of PHD2. [ABSTRACT FROM AUTHOR]

Transport of proteins between cytoplasm and nucleus is mediated by transport factors of the importin α- and β-families and occurs along a gradient of the small GTPase Ran. To date, in vivo analysis as well as prediction of protein nuclear export remain tedious and difficult. We generated a novel bipartite assay called NEX-TRAP (Nuclear EXport Trapped by RAPamycin) for in vivo analysis of protein nuclear export. The assay is based on the rapamycin-induced dimerization of the modules FRB ( FK506-rapamycin ( FR)-binding domain) and FKBP ( FK506-binding protein-12): a potential nuclear export cargo is fused to FRB, to EYFP for direct visualization as well as to an SV40-derived nuclear localization signal ( NLS) for constitutive nuclear import. An integral membrane protein that resides at the trans Golgi network ( TGN) is fused to a cytoplasmically exposed FKBP and serves as reporter. EYFP-NLS-FRB fusion proteins with export activity accumulate in the nucleus at steady state but continuously shuttle between nucleus and cytoplasm. Rapamycin-induced dimerization of FRB and FKBP at the TGN traps the shuttling protein outside of the nucleus, making nuclear export permanent. Using several example cargoes, we show that the NEX-TRAP is superior to existing assays owing to its ease of use, its sensitivity and accuracy. Analysis of large numbers of export cargoes is facilitated by recombinational cloning. The NEX-TRAP holds the promise of applicability in automated fluorescence imaging for systematic analysis of nuclear export, thereby improving in silico prediction of nuclear export sequences. [ABSTRACT FROM AUTHOR]

Abstract: WD repeat-containing protein 42A (WDR42A) is a member of the WD40-repeat proteins. Here, we investigated the localization pattern of WDR42A in living cells. By mutational analysis, a nuclear localization signal, 114PRRRVQRKR122, was for the first time determined. The dominant negative, co-immunoprecipitation and GST pull-down results further demonstrated that the nuclear import of WDR42A was mediated by karyopherin-α1/β1 in conjunction with the GTPase Ran. Additionally, a nuclear export signal, 39IEVEASDLSLSL50, was verified to be a functional NES, which mediated the nuclear export through Chromosome Region Maintenance 1 dependent pathway. All these data suggest WDR42A is a nucleocytoplasmic shuttling protein. Structured summary of protein interactions: Karyopherin alpha-1 physically interacts with WDR42A by anti tag co-immunoprecipitation (View interaction) WDR42A physically interacts with Karyopherin alpha-1 by pull down (View interaction) Karyopherin beta-1 physically interacts with WDR42A by anti tag co-immunoprecipitation (View interaction) WDR42A physically interacts with CRM1 by anti tag co-immunoprecipitation (View interaction) WDR42A and RAN colocalize by fluorescence microscopy (View interaction) [Copyright &y& Elsevier]

Background: ADP-ribosylation is a posttranslational modification catalyzed in cells by ADP-ribosyltransferases (ARTD or PARP enzymes). The ARTD family consists of 17 members. Some ARTDs modify their substrates by adding ADP-ribose in an iterative process, thereby synthesizing ADP-ribose polymers, the best-studied example being ARTD1/PARP1. Other ARTDs appear to mono-ADP-ribosylate their substrates and are unable to form polymers. The founding member of this latter subclass is ARTD10/PARP10, which we identified as an interaction partner of the nuclear oncoprotein MYC. Biochemically ARTD10 uses substrate-assisted catalysis to modify its substrates. Our previous studies indicated that ARTD10 may shuttle between the nuclear and cytoplasmic compartments. We have now addressed this in more detail. Results: We have characterized the subcellular localization of ARTD10 using live-cell imaging techniques. ARTD10 shuttles between the cytoplasmic and nuclear compartments. When nuclear, ARTD10 can interact with MYC as measured by bimolecular fluorescence complementation. The shuttling is controlled by a Crm1-dependent nuclear export sequence and a central ARTD10 region that promotes nuclear localization. The latter lacks a classical nuclear localization sequence and does not promote full nuclear localization. Rather this non-conventional nuclear localization sequence results in an equal distribution of ARTD10 between the cytoplasmic and the nuclear compartments. ARTD10 forms discrete and dynamic bodies primarily in the cytoplasm but also in the nucleus. These contain poly-ubiquitin and co-localize in part with structures containing the poly-ubiquitin receptor p62/ SQSTM1. The co-localization depends on the ubiquitin-associated domain of p62, which mediates interaction with poly-ubiquitin. Conclusions: Our findings demonstrate that ARTD10 is a highly dynamic protein. It shuttles between the nuclear and cytosolic compartments dependent on a classical nuclear export sequence and a domain that mediates nuclear uptake. Moreover ARTD10 forms discrete bodies that exchange subunits rapidly. These bodies associate at least in part with the poly-ubiquitin receptor p62. Because this protein is involved in the uptake of cargo into autophagosomes, our results suggest a link between the formation of ARTD10 bodies and autophagy. Post-translational modifications refer to changes in the chemical appearance of proteins and occur, as the name implies, after proteins have been synthesized. These modifications frequently affect the behavior of proteins, including alterations in their activity or their subcellular localization. One of these modifications is the addition of ADP-ribose to a substrate from the cofactor NAD+. The enzymes responsible for this reaction are ADP-ribosyltransferases (ARTDs or previously named PARPs). Presently we know very little about the role of mono-ADP-ribosylation of proteins that occurs in cells. We identified ARTD10, a mono-ADP-ribosyltransferase, as an interaction partner of the oncoprotein MYC. In this study we have analyzed how ARTD10 moves within a cell. By using different live-cell imaging technologies that allow us to follow the position of ARTD10 molecules over time, we found that ARTD10 shuttles constantly in and out of the nucleus. In the cytosol ARTD10 forms distinct structures or bodies that themselves are moving within the cell and that exchange ARTD10 subunits rapidly. We have identified the regions within ARTD10 that are required for these movements. Moreover we defined these bodies as structures that interact with p62. This protein is known to play a role in bringing other proteins to a structure referred to as the autophagosome, which is involved in eliminating debris in cells. Thus our work suggests that ARTD10 might be involved in and is regulated by ADP-riboslyation autophagosomal processes. [ABSTRACT FROM AUTHOR]

The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38, extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by which PKA causes nuclear export remains unsolved. In the study reported here we demonstrated that Ser-115 is an in vitro PKA phosphoacceptor site, and that PKA, but not p38, ERK3 or ERK4, is unable to redistribute MK5 S115A to the cytoplasm. However, the phosphomimicking MK5 S115D mutant resides in the cytoplasm in untreated cells. While p38, ERK3 and ERK4 fail to trigger nuclear export of the kinase dead T182A and K51E MK5 mutants, S115D/T182A and K51E/S115D mutants were able to enter the cytoplasm of resting cells. Finally, we demonstrated that mutations in Ser-115 affect the biological properties of MK5. Taken together, our results suggest that Ser-115 plays an essential role in PKA-regulated nuclear export of MK5, and that it also may regulate the biological functions of MK5. [ABSTRACT FROM AUTHOR]

In this work we analyze the dynamics of a quantum particle subject to an asymmetric bistable potential and interacting with a thermal reservoir. We obtain the time evolution of the population distributions in both energy and position eigenstates of the particle, for different values of the coupling strength with the thermal bath. The calculation is carried out using the Feynman-Vernon functional under the discrete variable representation. [ABSTRACT FROM AUTHOR]

This essay makes the argument that the numerous ‘‘networks’’ or ‘‘inter/intranetworks’’ that structure the video game industry have lived local effects for those involved in the production of video games. In particular, this is most visible in the realm of console video game development but is visible in many other contexts as well. It uses the Nintendo Entertainment System (NES) as an index into this complex and highly structured world that frequently disappears from developers perception. The essay uses largely historical data drawn from patent filings, Securities and Exchange Commission (SEC) filings, and court cases to analyze these networks. The essay argues that these inter/intranetworks, as constructed, have been instrumental in the way that the game industry now finds itself structured and that as the industry has ‘‘matured,’’ the networks have become less accessible and less interoperable. [ABSTRACT FROM PUBLISHER]

Pericentrin, a conserved centrosomal component, provides the structural scaffold to anchor numerous centrosomal proteins, and thus plays an essential role in the organization and function of the centrosome and the mitotic spindle. Although pericentrin was shown to localize in the cytoplasm and reported to be sensitive to leptomycin B (LMB), a specific inhibitor of Crm1, the regions within pericentrin that serve as signals for transporting in and out of the nucleus have not yet been identified. In this study, we identified five novel nuclear export signals (NESs) in pericentrin with diverse export activities. All of the five NESs could bind to Crm1 in a LMB-sensitive way when mediating the nuclear export of pericentrin. We also demonstrated that the region of amino acids 8-42 in pericentrin contains a tripartite nuclear localization signal (NLS) consisting of three clusters of basic amino acids. The NLS of pericentrin binds to importin β directly or via the adaptor importin α to form the import complex, which could be disrupted by RanQ69L, a dominant-negative Ran GTPase possessing high affinity for importin β. Furthermore, we found that mutation of the NESs in full-length pericentrin results in both nuclear and cytoplasmic localization, and mutation of the NLS abolishes the nuclear import of pericentrin. On the basis of these results, we suggest that the NESs and NLS of pericentrin are essential for its subcellular localization and nucleocytoplasmic trafficking during the cell cycle. [ABSTRACT FROM AUTHOR]

The karyopherin CRM1 mediates nuclear export of proteins and ribonucleoproteins bearing a leucine-rich nuclear export signal (NES). To elucidate the precise mechanism by which NES-cargos are dissociated from CRM1 in the cytoplasm, which is important for transport directionality, we determined a 2.0-Å resolution crystal structure of yeast CRM1:RanBP1:RanGTP complex, an intermediate in the disassembly of the CRM1 nuclear export complex. The structure shows that on association of Ran-binding domain (RanBD) of RanBP1 with CRM1:NES-cargo:RanGTP complex, RanBD and the C-terminal acidic tail of Ran induce a large movement of the intra-HEAT9 loop of CRM1. The loop moves to the CRM1 inner surface immediately behind the NES-binding site and causes conformational rearrangements in HEAT repeats 11 and 12 so that the hydrophobic NES-binding cleft on the CRM1 outer surface closes, squeezing out the NES-cargo. This allosteric mechanism accelerates dissociation of NES by over two orders of magnitude. Structure-based mutagenesis indicated that the HEAT9 loop also functions as an allosteric autoinhibitor to stabilize CRM1 in a conformation that is unable to bind NES-cargo in the absence of RanGTP. [ABSTRACT FROM AUTHOR]

P68 RNA helicase is a prototypical DEAD box RNA helicase. The protein plays a very important role in early organ development and maturation. Consistent with the function of the protein in transcriptional regulation and pre-mRNA splicing, p68 was found to predominately localize in the cell nucleus. However, recent experiments demonstrate a transient cytoplasmic localization of the protein. We report here that p68 shuttles between the nucleus and the cytoplasm. The nucleocytoplasmic shuttling of p68 is mediated by two nuclear localization signal and two nuclear exporting signal sequence elements. Our experiments reveal that p68 shuttles via a classical RanGTPase-dependent pathway. [ABSTRACT FROM AUTHOR]

Trafficking of proteins between the cytoplasm and nucleus occurs exclusively across the nuclear pore complex of eucaryotic cells. Fundamental aspects of this process affect temporal and spatial parameters, the latter carried out by specific import [nuclear localization sequence (NLS)] and export [nuclear export sequence (NES)] sequences. In this study, we focused on the adaptation of a protein heterodimerization assay to kinetically measure Crm1-mediated nuclear export in living cells using the rapalog AP21967, a heterodimerizing agent and NLS- and NES-containing fusion proteins equipped with distinct AP21967-specific binding motifs. In HeLa cells, we observed rapid nuclear export of the NLS-containing fusion protein in the presence of AP21967, with the extent of this process being a function of the number of AP21967-binding motifs. AP21967-induced nuclear export was specifically inhibited by the Crm1-binding molecule leptomycin B. Half maximal export was achieved after ∼ 10 min. We further applied protein heterodimerization in HeLa cells to study induced NLS-mediated nuclear import. Only in the presence of heterodimerizer AP21967 nuclear import of a cytoplasmically localizing fusion protein was observed. Induced protein heterodimerization is thus a valuable tool to quantitatively study nucleocytoplasmic protein trafficking in cultured cells, in a non-invasive, time-saving manner. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) remains the leading cause of cancer-related deaths with the lowest five-year survival rates among all of the human cancers. Multiple factors contribute to its poor outcome, including intratumor heterogeneity, along with migratory and invasive capacities of tumour cells. Over the last several years Doublecortin (DCX) has been one of the debatable factors influencing GBM cells' migration. To resolve DCX's ambiguous role in GBM cells' migration, we set to analyse the expression patterns of DCX along with Nestin (NES) and Oligodendrocyte lineage transcription factor 2 (OLIG2) in 17 cases of GBM, using immunohistochemistry, followed by an analysis of single-cell RNA-seq data. Our results showed that only a small subset of DCX positive (DCX+) cells was present in the tumour. Moreover, no particular pattern emerged when analysing DCX+ cells relative position to the tumour margin. By looking into single-cell RNA-seq data, the majority of DCX+ cells were classified as non-cancerous, with a small subset of cells that could be regarded as glioma stem cells. In conclusion, our findings support the notion that glioma cells express DCX; however, there is no clear evidence to prove that DCX participates in GBM cell migration. [ABSTRACT FROM AUTHOR]