bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity
Authors: Nunes Sofia C. , Ramos Cristiano , Lopes-Coelho Filipa , Sequeira Catarina O. , Silva Fernanda , Gouveia-Fernandes Sofia , Rodrigues Armanda , Guimarães António , Silveira Margarida , Abreu Sofia , Santo Vítor E. , Brito Catarina , Félix Ana , Pereira Sofia A. , Serpa Jacinta 
Published: June 2018

AbstractOvarian cancer is the second most common gynaecologic malignancy and the main cause of death from gynaecologic cancer, due to late diagnosis and chemoresistance. Studies have reported the role of cysteine in cancer, by contributing for hydrogen sulphide (H2S) generation and as a precursor of glutathione (GSH). However, the role of cysteine in the adaptation to hypoxia and therapy response remains unclear. We used several ovarian cancer cell lines, ES2, OVCAR3, OVCAR8, A2780 and A2780cisR, to clarify cysteine relevance in ovarian cancer cells survival upon hypoxia and carboplatin. Results show that ES2 and OVCAR8 cells presented a stronger dependence on cysteine availability upon hypoxia and carboplatin exposure than OVCAR3 cells. Interestingly, the A2780 cisR, but not A2780 parental cells, benefits from cysteine upon carboplatin exposure, showing that cysteine is crucial for chemoresistance. Moreover, GSH degradation and subsequent cysteine recycling pathway is associated with ovarian cancer as seen in peripheral blood serum from patients. Higher levels of total free cysteine (Cys) and homocysteine (HCys) were found in ovarian cancer patients in comparison with benign tumours and lower levels of GSH were found in ovarian neoplasms patients in comparison with healthy individuals. Importantly, the total and S-Homocysteinylated levels distinguished blood donors from patients with neoplasms as well as patients with benign from patients with malignant tumours. The levels of S-cysteinylated proteins distinguish blood donors from patients with neoplasms and the free levels of Cys in serum distinguish blood from patients with benign tumours from patients with malignant tumours. Herein we disclosed that cysteine contributes for a worse disease prognosis, allowing faster adaptation to hypoxia and protecting cells from carboplatin. The measurement of serum cysteine levels can be an effective tool for early diagnosis, for outcome prediction and follow up of disease progression.
Spatiotemporal disturbance characteristics determine functional stability and collapse risk of simulated microbial ecosystems
Authors: König Sara , Worrich Anja , Banitz Thomas , Centler Florian , Harms Hauke , Kästner Matthias , Miltner Anja , Wick Lukas Y. , Thullner Martin , Frank Karin 
Published: June 2018

AbstractTerrestrial microbial ecosystems are exposed to many types of disturbances varying in their spatial and temporal characteristics. The ability to cope with these disturbances is crucial for maintaining microbial ecosystem functions, especially if disturbances recur regularly. Thus, understanding microbial ecosystem dynamics under recurrent disturbances and identifying drivers of functional stability and thresholds for functional collapse is important. Using a spatially explicit ecological model of bacterial growth, dispersal, and substrate consumption, we simulated spatially heterogeneous recurrent disturbances and investigated the dynamic response of pollutant biodegradation – exemplarily for an important ecosystem function. We found that thresholds for functional collapse are controlled by the combination of disturbance frequency and spatial configuration (spatiotemporal disturbance regime). For rare disturbances, the occurrence of functional collapse is promoted by low spatial disturbance fragmentation. For frequent disturbances, functional collapse is almost inevitable. Moreover, the relevance of bacterial growth and dispersal for functional stability also depends on the spatiotemporal disturbance regime. Under disturbance regimes with moderate severity, microbial properties can strongly affect functional stability and shift the threshold for functional collapse. Similarly, networks facilitating bacterial dispersal can delay functional collapse. Consequently, measures to enhance or sustain bacterial growth/dispersal are promising strategies to prevent functional collapses under moderate disturbance regimes.
A Data Driven Model for Predicting RNA-Protein Interactions based on Gradient Boosting Machine
Authors: Jain Dharm Skandh , Gupte Sanket Rajan , Aduri Raviprasad 
Published: June 2018

AbstractRNA protein interactions (RPI) play a pivotal role in the regulation of various biological processes. Experimental validation of RPI has been time-consuming, paving the way for computational prediction methods. The major limiting factor of these methods has been the accuracy and confidence of the predictions, and our in-house experiments show that they fail to accurately predict RPI involving short RNA sequences such as TERRA RNA. Here, we present a data-driven model for RPI prediction using a gradient boosting classifier. Amino acids and nucleotides are classified based on the high-resolution structural data of RNA protein complexes. The minimum structural unit consisting of five residues is used as the descriptor. Comparative analysis of existing methods shows the consistently higher performance of our method irrespective of the length of RNA present in the RPI. The method has been successfully applied to map RPI networks involving both long noncoding RNA as well as TERRA RNA. The method is also shown to successfully predict RNA and protein hubs present in RPI networks of four different organisms. The robustness of this method will provide a way for predicting RPI networks of yet unknown interactions for both long noncoding RNA and microRNA.
Nintedanib inhibits growth of human prostate carcinoma cells by modulating both cell cycle and angiogenesis regulators
Authors: da Silva Raquel Frenedoso , Dhar Deepanshi , Raina Komal , Kumar Dileep , Kant Rama , Cagnon Valeria Helena Alves , Agarwal Chapla , Agarwal Rajesh 
Published: June 2018

AbstractProstate cancer (PCa) is the most common malignancy and second leading cause of cancer-related deaths in American men. Proliferating cells have higher need for nutrients and oxygen, triggering angiogenesis that plays a critical role in tumor growth, progression and metastasis. Consequently, immense focus has converged onto inhibitors of angiogenesis in cancer treatment, such as Nintedanib, which has shown exceptional antitumor activity via inhibiting cell proliferation and the resulting tumor growth, primarily due to its combined action on tumor cells, endothelial cells and pericytes. Accordingly, here we assessed both in vitro and in vivo efficacy of Nintedanib in PCa. The results showed that Nintedanib decreased cell viability in both androgen dependent- and -independent PCa cells, together with a decrease in cell motility and invasiveness. Nintedanib also reduced the expression of significant genes responsible for cell cycle progression. PCa PC3 xenograft-carrying nude mice treated with Nintedanib showed significantly decreased tumor volume and cell proliferation alongside diminished levels of pro-angiogenic molecules and blood vessel densities. In conclusion, we report that Nintedanib has strong efficacy against PCa in pre-clinical models via modulation of various pathways, and that it could be employed as a promising new strategy to manage PCa clinically.
Determination of the size distribution of non-spherical nanoparticles by electric birefringence-based methods
Authors: Arenas-Guerrero Paloma , Delgado Ángel V. , Donovan Kevin J. , Scott Kenneth , Bellini Tommaso , Mantegazza Francesco , Jiménez María L. 
Published: June 2018

AbstractThe in situ determination of the size distribution of dispersed non-spherical nanoparticles is an essential characterization tool for the investigation and use of colloidal suspensions. In this work, we test a size characterization method based on the measurement of the transient behaviour of the birefringence induced in the dispersions by pulsed electric fields. The specific shape of such relaxations depends on the distribution of the rotational diffusion coefficient of the suspended particles. We analyse the measured transient birefringence with three approaches: the stretched-exponential, Watson-Jennings, and multi-exponential methods. These are applied to six different types of rod-like and planar particles: PTFE rods, goethite needles, single- and double-walled carbon nanotubes, sodium montmorillonite particles and gibbsite platelets. The results are compared to electron microscopy and dynamic light scattering measurements. The methods here considered provide good or excellent results in all cases, proving that the analysis of the transient birefringence is a powerful tool to obtain complete size distributions of non-spherical particles in suspension.
Rapid recombinant protein expression in cell-free extracts from human blood
Authors: Burgenson David , Gurramkonda Chandrasekhar , Pilli Manohar , Ge Xudong , Andar Abhay , Kostov Yordan , Tolosa Leah , Rao Govind 
Published: June 2018

AbstractSeveral groups have recently reported on the utility of cell-free expression systems to make therapeutic proteins, most of them employing CHO or E. coli cell-free extracts. Here, we propose an alternative that uses human blood derived leukocyte cell extracts for the expression of recombinant proteins. We demonstrate expression of nano luciferase (Nluc), Granulocyte-colony stimulating factor (G-CSF) and Erythropoietin (EPO) in cell-free leukocyte extracts within two hours. Human blood is readily available from donors and blood banks and leukocyte rich fractions are easy to obtain. The method described here demonstrates the ability to rapidly express recombinant proteins from human cell extracts that could provide the research community with a facile technology to make their target protein. Eventually, we envision that any recombinant protein can be produced from patient-supplied leukocytes, which can then be injected back into the patient. This approach could lead to an alternative model for personalized medicines and vaccines.
Precisely dating the Frasnian–Famennian boundary: implications for the cause of the Late Devonian mass extinction
Authors: Percival L. M. E. , Davies J. H. F. L. , Schaltegger U. , De Vleeschouwer D. , Da Silva A.-C. , Föllmi K. B. 
Published: June 2018

AbstractThe Frasnian–Famennian boundary records one of the most catastrophic mass extinctions of the Phanerozoic Eon. Several possible causes for this extinction have been suggested, including extra-terrestrial impacts and large-scale volcanism. However, linking the extinction with these potential causes is hindered by the lack of precise dating of either the extinction or volcanic/impact events. In this study, a bentonite layer in uppermost-Frasnian sediments from Steinbruch Schmidt (Germany) is re-analysed using CA-ID-TIMS U-Pb zircon geochronology in order to constrain the date of the Frasnian–Famennian extinction. A new age of 372.36 ± 0.053 Ma is determined for this bentonite, confirming a date no older than 372.4 Ma for the Frasnian–Famennian boundary, which can be further constrained to 371.93–371.78 Ma using a pre-existing Late Devonian age model. This age is consistent with previous dates, but is significantly more precise. When compared with published ages of the Siljan impact crater and basalts produced by large-scale volcanism, there is no apparent correlation between the extinction and either phenomenon, not clearly supporting them as a direct cause for the Frasnian–Famennian event. This result highlights an urgent need for further Late Devonian geochronological and chemostratigraphic work to better understand the cause(s) of this extinction.
GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling
Authors: Khanna Puja , Lee Joan Shuying , Sereemaspun Amornpun , Lee Haeryun , Baeg Gyeong Hun 
Published: June 2018

AbstractDysregulated JAK/STAT signaling has been implicated in breast cancer metastasis, which is associated with high relapse risks. However, mechanisms underlying JAK/STAT signaling-mediated breast tumorigenesis are poorly understood. Here, we showed that GRAMD1B expression is upregulated on IL-6 but downregulated upon treatment with the JAK2 inhibitor AG490 in the breast cancer MDA-MB-231 cells. Notably, Gramd1b knockdown caused morphological changes of the cells, characterized by the formation of membrane ruffling and protrusions, implicating its role in cell migration. Consistently, GRAMD1B inhibition significantly enhanced cell migration, with an increase in the levels of the Rho family of GTPases. We also found that Gramd1b knockdown-mediated pro-migratory phenotype is associated with JAK2/STAT3 and Akt activation, and that JAK2 or Akt inhibition efficiently suppresses the phenotype. Interestingly, AG490 dose-dependently increased p-Akt levels, and our epistasis analysis suggested that the effect of JAK/STAT inhibition on p-Akt is via the regulation of GRAMD1B expression. Taken together, our results suggest that GRAMD1B is a key signaling molecule that functions to inhibit cell migration in breast cancer by negating both JAK/STAT and Akt signaling, providing the foundation for its development as a novel biomarker in breast cancer.
Effect of Donor-Acceptor Vertical Composition Profile on Performance of Organic Bulk Heterojunction Solar Cells
Authors: Bi Sheng , Ouyang Zhongliang , Shaik Shoieb , Li Dawen 
Published: June 2018

AbstractIn organic bulk heterojunction solar cells (OSCs) donor-acceptor vertical composition profile is one of the crucial factors that affect power-conversion efficiency (PCE). In this simulation study, five different kinds of donor-acceptor vertical configurations, including sandwich type I and type II, charge transport favorable, charge transport unfavorable, and uniform vertical distribution, have been investigated for both regular and inverted OSC structures. OSCs with uniform and charge transport favorable vertical composition profiles demonstrate the highest efficiencies. High PCE from charge transport favorable configuration can be attributed to low recombination because of facilitated charge transport in active layer and collection at electrodes, while high PCE from uniform structure is due to sufficient interfaces for efficient exciton dissociation. OSCs with sandwich and charge transport unfavorable structures show much lower efficiencies. The physical mechanisms behind simulation results are explained based on energy band diagrams, dark current-voltage characteristics, and comparison of external quantum efficiency. In conclusion, experimental optimization of vertical composition profile should be directed to either uniform or charge transport favorable vertical configurations in order to achieve high-performance OSCs.
Highly-coherent stimulated phonon oscillations in a multi-core optical fiber
Authors: Diamandi H. Hagai , London Yosef , Bashan Gil , Bergman Arik , Zadok Avi 
Published: June 2018

AbstractOpto-mechanical oscillators that generate coherent acoustic waves are drawing much interest, in both fundamental research and applications. Narrowband oscillations can be obtained through the introduction of feedback to the acoustic wave. Most previous realizations of this concept, sometimes referred to as “phonon lasers”, relied on radiation pressure and moving boundary effects in micro- or nano-structured media. Demonstrations in bulk crystals required cryogenic temperatures. In this work, stimulated emission of highly-coherent acoustic waves is achieved in a commercially-available multi-core fiber, at room temperature. The fiber is connected within an opto-electronic cavity loop. Pump light in one core is driving acoustic waves via electrostriction, whereas an optical probe wave at a different physical core undergoes photo-elastic modulation by the stimulated acoustic waves. Coupling between pump and probe is based entirely on inter-core, opto-mechanical cross-phase modulation: no direct optical feedback is provided. Single-frequency mechanical oscillations at hundreds of MHz frequencies are obtained, with side-mode suppression that is better than 55 dB. A sharp threshold and rapid collapse of the linewidth above threshold are observed. The linewidths of the acoustic oscillations are on the order of 100 Hz, orders of magnitude narrower than those of the pump and probe light sources. The relative Allan’s deviation of the frequency is between 0.1–1 ppm. The frequency may be switched among several values by propagating the pump or probe waves in different cores. The results may be used in sensing, metrology and microwave-photonic information processing applications.
Subependymomas – Characteristics of a “Leave me Alone” Lesion
Authors: Kammerer Sara , Mueller-Eschner Monika , Lauer Arne , Luger Anna-Luisa , Quick-Weller Johanna , Franz Kea , Harter Patrick , Berkefeld Joachim , Wagner Marlies 
Published: June 2018

Purpose Intracranial subependymomas are rare, mostly asymptomatic tumours, which are often found incidentally and therefore did not receive much attention in previous literature. By being classified as benign grade I in the WHO classification of tumours of the central nervous system, they are given a special status compared to the other ependymal tumours. Tumor recurrences are a rarity, spinal “drop metastases” do not occur. While etiological, pathological and therapeutic characteristics have been subject of several publications over the last few decades and have meanwhile been well studied, the imaging characteristics are much less well received.
Material and method Retrospective analysis of our relatively large group of 33 patients with subependymoma, including 4 patients with a mixture of subependymomas with ependymal cell fractions in terms of imaging and clinical aspects and with reference to a current literature review.
Results Subependymomas have typical image morphologic characteristics that differentiate them from tumors of other entities, however, the rare subgroup of histopathological mixtures of subependymomas with ependymal cell fractions has no distinctly different imaging properties.
Conclusions Knowing the imaging characteristics of subpendymoma and their differential diagnoses is of particular importance in order to be able to decide between the necessity of follow-up controls, an early invasive diagnosis or, depending on the entity, tumor resection.
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Citation Format
Antimicrobial and Efflux Inhibitor Activity of Usnic Acid Against Mycobacterium abscessus
Authors: Ramis Ivy , Vianna Júlia , Reis Ana , von Groll Andrea , Ramos Daniela , Viveiros Miguel , da Silva Pedro 
Published: June 2018

AbstractNew drugs are needed to treat infections with antimicrobial-resistant Mycobacterium abscessus; therefore, we evaluated usnic acid as an antimicrobial agent and efflux inhibitor (EI) against M. abscessus. Usnic acid showed antimicrobial activity, and synergistically, the EI verapamil increased this activity. In addition, when we evaluated the interaction of antimicrobials with usnic acid, the increase of their activity was observed. Finally, usnic acid showed an efflux inhibitory effect between the classical EIs verapamil and carbonyl cyanide m-chlorophenylhydrazine. In conclusion, usnic acid showed both antimicrobial and EI activity, indicating that this natural compound may be a promising scaffold for new drugs against this difficult-to-treat microorganism.
Recommendations for the Use of Testosterone in Male Transgender
Authors: Costa Laura Bregieiro Fernandes , Rosa-e-Silva Ana Carolina Japur de Sá , Medeiros Sebastião Freitas de , Nacul Andrea Prestes , Carvalho Bruno Ramalho de , Benetti-Pinto Cristina Laguna , Yela Daniela Angerame , Maciel Gustavo Arantes Rosa , Soares Júnior José Maria , Maranhão Técia Maria de Oliveira 
Published: June 2018

AbstractGender incongruence is defined as a condition in which an individual self-identifies and desires to have physical characteristics and social roles that connote the opposite biological sex. Gender dysphoria is when an individual displays the anxiety and/or depression disorders that result from the incongruity between the gender identity and the biological sex. The gender affirmation process must be performed by a multidisciplinary team. The main goal of the hormone treatment is to start the development of male physical characteristics by means of testosterone administration that may be offered to transgender men who are 18 years old or over. The use of testosterone is usually well tolerated and improves the quality of life. However, there is still lack of evidence regarding the effects and risks of the long-term use of this hormone. Many different pharmacological formulations have been used in the transsexualization process. The most commonly used formulation is the intramuscular testosterone esters in a short-term release injection, followed by testosterone cypionate or testosterone enanthate. In the majority of testosterone therapy protocols, the male physical characteristics can be seen in almost all users after 6 months of therapy, and the maximum virilization effects are usually achieved after 3 to 5 years of regular use of the hormone. To minimize risks, plasmatic testosterone levels should be kept within male physiological ranges (300 to 1,000 ng/dl) during hormonal treatment. It is recommended that transgender men under androgen therapy be monitored every 3 months during the 1st year of treatment and then, every 6 to 12 months.
Methane in groundwater before, during, and after hydraulic fracturing of the Marcellus Shale
Authors: Barth-Naftilan E. , Sohng J. , Saiers J. E. 
Published: June 2018

Significance
This study incorporates time series sampling of groundwater before, during, and after drilling, hydraulic fracturing, and initiation of shale gas production. Using monitoring wells installed next to gas well pads and above gas well laterals, previously undocumented responses to drilling and a gas well casing breach were observed, although groundwater impacts arising from the process of hydraulic fracturing were not detected. We discover considerable temporal variability in methane concentrations in deeper horizons of freshwater aquifers and attribute this to persistent shifts in aquifer recharge that influence mixing between shallow freshwater and comparatively saline and methane-rich deep groundwater. These results have implications for attribution of groundwater contamination to specific stages of shale gas development or natural processes and improving regulatory monitoring.
Accelerating pathway evolution by increasing the gene dosage of chromosomal segments
Authors: Tumen-Velasquez Melissa , Johnson Christopher W. , Ahmed Alaa , Dominick Graham , Fulk Emily M. , Khanna Payal , Lee Sarah A. , Schmidt Alicia L. , Linger Jeffrey G. , Eiteman Mark A. , Beckham Gregg T. , Neidle Ellen L. 
Published: June 2018

SignificanceGene duplication and divergence are cornerstones of evolution. Genetic redundancy resulting from repeated DNA provides flexibility for transient changes in copy number that may confer selective benefit under new or changing environmental conditions. This work describes a method for creating tandem arrays of specific DNA segments in a bacterium,Acinetobacter baylyi, to accelerate experimental evolution. The induced chromosomal gene amplification mimics a natural process that would otherwise occur more slowly and stochastically. The success of this approach for the evolution of novel protein function was demonstrated with studies of an enzyme that has bioenergy applications in lignin valorization. A protein variant, which emerged from Evolution by Amplification and Synthetic biology, is beneficial in a different bacterium, indicating the broad utility of the method.