bluuebunny/crossref_metadata_2025_split huggingface dataset:
BTK: a two-faced effector in cancer and tumour suppression
Authors: Rada Miran , Barlev Nickolai , Macip Salvador 
Published: October 2018

AbstractMany genes of the human genome display pleiotropic activity, playing an important role in two or more unrelated pathways. Surprisingly, some of these functions can even be antagonistic, often letting to divergent functional outcomes depending on microenviromental cues and tissue/cell type-dependent parameters. Lately, the Bruton’s tyrosine kinase (BTK) has emerged as one of such pleiotropic genes, with opposing effects in cancer pathways. While it has long been considered oncogenic in the context of B cell malignancies, recent data shows that BTK can also act as a tumour suppressor in other cells, as an essential member of the p53 and p73 responses to damage. Since BTK inhibitors are already being used clinically, it is important to carefully review these new findings in order to fully understand the consequences of blocking BTK activity in all the cells of the organism.
DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity
Authors: Lin Xin-Xuan , Sen Ilke , Janssens Georges E. , Zhou Xin , Fonslow Bryan R. , Edgar Daniel , Stroustrup Nicholas , Swoboda Peter , Yates John R. , Ruvkun Gary , Riedel Christian G. 
Published: October 2018

AbstractThe ability to perceive and respond to harmful conditions is crucial for the survival of any organism. The transcription factor DAF-16/FOXO is central to these responses, relaying distress signals into the expression of stress resistance and longevity promoting genes. However, its sufficiency in fulfilling this complex task has remained unclear. Using C. elegans, we show that DAF-16 does not function alone but as part of a transcriptional regulatory module, together with the transcription factor HLH-30/TFEB. Under harmful conditions, both transcription factors translocate into the nucleus, where they often form a complex, co-occupy target promoters, and co-regulate many target genes. Interestingly though, their synergy is stimulus-dependent: They rely on each other, functioning in the same pathway, to promote longevity or resistance to oxidative stress, but they elicit heat stress responses independently, and they even oppose each other during dauer formation. We propose that this module of DAF-16 and HLH-30 acts by combinatorial gene regulation to relay distress signals into the expression of specific target gene sets, ensuring optimal survival under each given threat.
Raising the redox potential in carboxyphenolate-based positive organic materials via cation substitution
Authors: Jouhara Alia , Dupré Nicolas , Gaillot Anne-Claire , Guyomard Dominique , Dolhem Franck , Poizot Philippe 
Published: October 2018

AbstractMeeting the ever-growing demand for electrical storage devices requires both superior and “greener” battery technologies. Nearly 40 years after the discovery of conductive polymers, long cycling stability in lithium organic batteries has now been achieved. However, the synthesis of high-voltage lithiated organic cathode materials is rather challenging, so very few examples of all-organic lithium-ion cells currently exist. Herein, we present an inventive chemical approach leading to a significant increase of the redox potential of lithiated organic electrode materials. This is achieved by tuning the electronic effects in the redox-active organic skeleton thanks to the permanent presence of a spectator cation in the host structure exhibiting a high ionic potential (or electronegativity). Thus, substituting magnesium (2,5-dilithium-oxy)-terephthalate for lithium (2,5-dilithium-oxy)-terephthalate enables a voltage gain of nearly +800 mV. This compound being also able to act as negative electrode via the carboxylate functional groups, an all-organic symmetric lithium-ion cell exhibiting an output voltage of 2.5 V is demonstrated.
Physical reality of the Preisach model for organic ferroelectrics
Authors: Urbanavičiūtė Indrė , Cornelissen Tim D. , Meng Xiao , Sijbesma Rint P. , Kemerink Martijn 
Published: October 2018

AbstractThe Preisach model has been a cornerstone in the fields of ferromagnetism and ferroelectricity since its inception. It describes a real, non-ideal, ferroic material as the sum of a distribution of ideal ‘hysterons’. However, the physical reality of the model in ferroelectrics has been hard to establish. Here, we experimentally determine the Preisach (hysteron) distribution for two ferroelectric systems and show how its broadening directly relates to the materials’ morphology. We connect the Preisach distribution to measured microscopic switching kinetics that underlay the macroscopic dispersive switching kinetics as commonly observed for practical ferroelectrics. The presented results reveal that the in principle mathematical construct of the Preisach model has a strong physical basis and is a powerful tool to explain polarization switching at all time scales in different types of ferroelectrics. These insights lead to guidelines for further advancement of the ferroelectric materials both for conventional and multi-bit data storage applications.
Slc7a5 regulates Kv1.2 channels and modifies functional outcomes of epilepsy-linked channel mutations
Authors: Baronas Victoria A. , Yang Runying Y. , Morales Luis Carlos , Sipione Simonetta , Kurata Harley T. 
Published: October 2018

AbstractKv1.2 is a prominent voltage-gated potassium channel that influences action potential generation and propagation in the central nervous system. We explored multi-protein complexes containing Kv1.2 using mass spectrometry followed by screening for effects on Kv1.2. We report that Slc7a5, a neutral amino acid transporter, has a profound impact on Kv1.2. Co-expression with Slc7a5 reduces total Kv1.2 protein, and dramatically hyperpolarizes the voltage-dependence of activation by −47 mV. These effects are attenuated by expression of Slc3a2, a known binding partner of Slc7a5. The profound Slc7a5-mediated current suppression is partly explained by a combination of gating effects including accelerated inactivation and a hyperpolarizing shift of channel activation, causing channels to accumulate in a non-conducting state. Two recently reported Slc7a5 mutations linked to neurodevelopmental delay exhibit a localization defect and have attenuated effects on Kv1.2. In addition, epilepsy-linked gain-of-function Kv1.2 mutants exhibit enhanced sensitivity to Slc7a5.
Inherent potential of steelmaking to contribute to decarbonisation targets via industrial carbon capture and storage
Authors: Tian Sicong , Jiang Jianguo , Zhang Zuotai , Manovic Vasilije 
Published: October 2018

AbstractAccounting for ~8% of annual global CO2 emissions, the iron and steel industry is expected to undertake the largest contribution to industrial decarbonisation. Despite the launch of several national and regional programmes for low-carbon steelmaking, the techno-economically feasible options are still lacking. Here, based on the carbon capture and storage (CCS) strategy, we propose a new decarbonisation concept which exploits the inherent potential of the iron and steel industry through calcium-looping lime production. We find that this concept allows steel mills to reach the 2050 decarbonisation target by 2030. Moreover, only this concept is revealed to exhibit a CO2 avoidance cost (12.5–15.8 €2010/t) lower than the projected CO2 trading price in 2020, whilst the other considered options are not expected to be economically feasible until 2030. We conclude that the proposed concept is the best available option for decarbonisation of this industrial sector in the mid- to long-term.
Measuring macromolecular size distributions and interactions at high concentrations by sedimentation velocity
Authors: Chaturvedi Sumit K. , Ma Jia , Brown Patrick H. , Zhao Huaying , Schuck P. 
Published: October 2018

AbstractIn concentrated macromolecular solutions, weak physical interactions control the solution behavior including particle size distribution, aggregation, liquid-liquid phase separation, or crystallization. This is central to many fields ranging from colloid chemistry to cell biology and pharmaceutical protein engineering. Unfortunately, it is very difficult to determine macromolecular assembly states and polydispersity at high concentrations in solution, since all motion is coupled through long-range hydrodynamic, electrostatic, steric, and other interactions, and scattering techniques report on the solution structure when average interparticle distances are comparable to macromolecular dimensions. Here we present a sedimentation velocity technique that, for the first time, can resolve macromolecular size distributions at high concentrations, by simultaneously accounting for average mutual hydrodynamic and thermodynamic interactions. It offers high resolution and sensitivity of protein solutions up to 50 mg/ml, extending studies of macromolecular solution state closer to the concentration range of therapeutic formulations, serum, or intracellular conditions.
Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability
Authors: Jing Anqi , Vizeacoumar Frederick S. , Parameswaran Sreejit , Haave Bjorn , Cunningham Chelsea E. , Wu Yuliang , Arnold Roland , Bonham Keith , Freywald Andrew , Han Jie , Vizeacoumar Franco J. 
Published: October 2018

AbstractCan transcriptomic alterations drive the evolution of tumors? We asked if changes in gene expression found in all patients arise earlier in tumor development and can be relevant to tumor progression. Our analyses of non-mutated genes from the non-amplified regions of the genome of 158 triple-negative breast cancer (TNBC) cases identified 219 exclusively expression-altered (EEA) genes that may play important role in TNBC. Phylogenetic analyses of these genes predict a “punctuated burst” of multiple gene upregulation events occurring at early stages of tumor development, followed by minimal subsequent changes later in tumor progression. Remarkably, this punctuated burst of expressional changes is instigated by hypoxia-related molecular events, predominantly in two groups of genes that control chromosomal instability (CIN) and those that remodel tumor microenvironment (TME). We conclude that alterations in the transcriptome are not stochastic and that early-stage hypoxia induces CIN and TME remodeling to permit further tumor evolution.
Entropy Measures of Human Communication Dynamics
Authors: Kulisiewicz Marcin , Kazienko Przemysław , Szymanski Boleslaw K. , Michalski Radosław 
Published: October 2018

AbstractHuman communication is commonly represented as a temporal social network, and evaluated in terms of its uniqueness. We propose a set of new entropy-based measures for human communication dynamics represented within the temporal social network as event sequences. Using real world datasets and random interaction series of different types we find that real human contact events always significantly differ from random ones. This human distinctiveness increases over time and by means of the proposed entropy measures, we can observe sociological processes that take place within dynamic communities.
Interplay between correlations and Majorana mode in proximitized quantum dot
Authors: Górski G. , Barański J. , Weymann I. , Domański T. 
Published: October 2018

AbstractWe study the low energy spectrum and transport properties of a correlated quantum dot coupled between normal and superconducting reservoirs and additionally hybridized with a topological superconducting nanowire, hosting the Majorana end-modes. In this setup the Majorana quasiparticle leaking into the quantum dot can be confronted simultaneously with the on-dot pairing and correlations. We study this interplay, focusing on the quantum phase transition from the spinless (BCS-type) to the spinful (singly occupied) configuration, where the subgap Kondo effect may arise. Using the selfconsistent perturbative treatment for correlations and the unbiased numerical renormalization group calculations we find that the Majorana mode has either constructive or destructive effect on the low-energy transport behavior of the quantum dot, depending on its spin. This spin-selective influence could be verified by means of the polarized STM spectroscopy.
Contribution of hurricane-induced sediment resuspension to coastal oxygen dynamics
Authors: Bianucci Laura , Balaguru Karthik , Smith Richard W. , Leung L. Ruby , Moriarty Julia M. 
Published: October 2018

AbstractHurricanes passing over the ocean can mix the water column down to great depths and resuspend massive volumes of sediments on the continental shelves. Consequently, organic carbon and reduced inorganic compounds associated with these sediments can be resuspended from anaerobic portions of the seabed and re-exposed to dissolved oxygen (DO) in the water column. This process can drive DO consumption as sediments become oxidized. Previous studies have investigated the effect of hurricanes on DO in different coastal regions of the world, highlighting the alleviation of hypoxic conditions by extreme winds, which drive vertical mixing and re-aeration of the water column. However, the effect of hurricane-induced resuspended sediments on DO has been neglected. Here, using a diverse suite of datasets for the northern Gulf of Mexico, we find that in the few days after a hurricane passage, decomposition of resuspended shelf sediments consumes up to a fifth of the DO added to the bottom of the water column during vertical mixing. Despite uncertainty in this value, we highlight the potential significance of this mechanism for DO dynamics. Overall, sediment resuspension likely occurs over all continental shelves affected by tropical cyclones, potentially impacting global cycles of marine DO and carbon.
The association between heart rhythm complexity and the severity of abdominal aorta calcification in peritoneal dialysis patients
Authors: Tsai Cheng-Hsuan , Lin Chen , Ho Yi-Heng , Lo Men-Tzung , Liu Li-Yu Daisy , Lin Chih-Ting , Huang Jenq-Wen , Peng Chung-Kang , Lin Yen-Hung 
Published: October 2018

AbstractAbdominal aorta calcification (AAC) has been associated with clinical outcomes in peritoneal dialysis (PD) patients. Heart rhythm complexity analysis has been shown to be a promising tool to predict outcomes in patients with cardiovascular disease. In this study, we aimed to analyze the association between heart rhythm complexity and AAC in PD patients. We prospectively analyzed 133 PD patients. Heart rhythm complexity including detrended fluctuation analysis and multiscale entropy was performed. In linear analysis, the patients in the higher AAC group (AAC ≥15%) had a significantly lower standard deviation of normal RR intervals, very low frequency, low frequency, high frequency and low/high frequency ratio. In non-linear analysis, DFAα1, slope 1–5, scale 5 and area 6–20 were significantly lower in the patients with higher AAC. Receiver operating characteristic curve analysis showed that DFAα1 had the greatest discriminatory power to differentiate these two groups. Multivariate logistic regression analysis showed that DFAα1 and HbA1c were significantly associated with higher AAC ratio. Adding DFAα1 significantly improved the discriminatory power of the linear parameters in both net reclassification improvement and integrated discrimination improvement models. In conclusion, DFAα1 is highly associated with AAC and a potential cardiovascular marker in PD patients.
Analysis of the relationship between the KRAS G12V oncogene and the Hippo effector YAP1 in embryonal rhabdomyosarcoma
Authors: Mohamed Abdalla D. , Shah Nupur , Hettmer Simone , Vargesson Neil , Wackerhage Henning 
Published: October 2018

AbstractPersistent hyperactivity of the Hippo effector YAP in activated satellite cells is sufficient to cause embryonal rhabdomyosarcoma (ERMS) in mice. In humans, YAP is abundant and nuclear in the majority of ERMS cases, and high YAP expression is associated with poor survival. However, YAP1 is rarely mutated in human ERMS. Instead, the most common mutations in ERMS are oncogenic RAS mutations. First, to compare YAP1S127A and KRASG12V-driven rhabdomyosarcomas, we re-analysed gene expression microarray datasets from mouse rhabdomyosarcomas caused by these genes. This revealed that only 20% of the up or downregulated genes are identical, suggesting substantial differences in gene expression between YAP and KRAS-driven rhabdomyosarcomas. As oncogenic RAS has been linked to YAP in other types of cancer, we also tested whether KRAS G12V alone or in combination with loss of p53 and p16 activates YAP in myoblasts. We found that neither KRAS G12V alone nor KRAS G12V combined with loss of p53 and p16 activated Yap or Yap/Taz-Tead1–4 transcriptional activity in C2C12 myoblasts or U57810 cells. In conclusion, whilst oncogenic KRAS mutation might activate Yap in other cell types, we could find no evidence for this in myoblasts because the expression of KRAS G12V expression did not change Yap/Taz activity in myoblasts and there was a limited overlap in gene expression between KRAS G12V and YAP1 S127A-driven tumours.
Population estimates of Bornean orang-utans using Bayesian analysis at the greater Batang Ai-Lanjak-Entimau landscape in Sarawak, Malaysia
Authors: Pandong Joshua , Gumal Melvin , Alen Lukmann , Sidu Ailyn , Ng Sylvia , Koh Lian Pin 
Published: October 2018

AbstractThe integration of Bayesian analysis into existing great ape survey methods could be used to generate precise and reliable population estimates of Bornean orang-utans. We used the Marked Nest Count (MNC) method to count new orang-utan nests at seven previously undocumented study sites in Sarawak, Malaysia. Our survey teams marked new nests on the first survey and revisited the plots on two more occasions; after about 21 and 42 days respectively. We used theN-mixture models to integrate suitability, abundance and detection models which account for zero inflation and imperfect detection for the analysis. The result was a combined estimate of 355 orang-utans with the 95% highest density interval (HDI) of 135 to 602 individuals. We visually inspected the posterior distributions of our parameters and compared precisions between study sites. We subsequently assess the strength or reliability of the generated estimates using identifiability tests. Only three out of the seven estimates had <35% overlap to indicate strong reliability. We discussed the limitations and advantages of our study design, and made recommendations to improve the sampling scheme. Over the course of this research, two of the study sites were gazetted as extensions to the Lanjak-Entimau Wildlife Sanctuary for orang-utan conservation.
Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models
Authors: Sechi Mario , Lall Rahul K. , Afolabi Saheed O , Singh Anant , Joshi Dinesh C. , Chiu Shing-Yan , Mukhtar Hasan , Syed Deeba N. 
Published: October 2018

AbstractThe anti-proliferative activity of dietary flavonoid fisetin has been validated in various cancer models. Establishing its precise mechanism of action has proved somewhat challenging given the multiplicity of its targets. We demonstrated that YB-1 promotes epithelial-to-mesenchymal transition and its inhibition suppressed tumor cell proliferation and invasion. The p90 ribosomal S6 kinase (RSK), an important ERK effector, activates YB-1 to drive melanoma growth. We found that fisetin treatment of monolayer/3-D melanoma cultures resulted in YB-1 dephosphorylation and reduced transcript levels. In parallel, fisetin suppressed mesenchymal markers and matrix-metalloproteinases in melanoma cells. Data from cell-free/cell-based systems indicated that fisetin inhibited RSK activity through binding to the kinase. Affinity studies for RSK isoforms evaluated stronger interaction for RSK2 than RSK1. Competition assays performed to monitor binding responses revealed that YB-1 and RSK2 do not compete, rather binding of fisetin to RSK2 promotes its binding to YB-1. Fisetin suppressed YB-1/RSK signaling independent of its effect on ERK, and reduced MDR1 levels. Comparable efficacy of fisetin and vemurafenib for inhibiting melanoma growth was noted albeit through divergent modulation of ERK. Our studies provide insight into additional modes of regulation through which fisetin interferes with melanoma growth underscoring its potential therapeutic efficacy in disease progression.
Enrichment and Quantification of Epitope-specific CD4+ T Lymphocytes using Ferromagnetic Iron-gold and Nickel Nanowires
Authors: Shore Daniel E. , Dileepan Thamotharampillai , Modiano Jaime F. , Jenkins Marc K. , Stadler Bethanie J. H. 
Published: October 2018

AbstractEpitope-specific CD4+ T lymphocytes were magnetically enriched using ferromagnetic Ni and Fe-Au nanowires coated with a monomer containing a major histocompatibility complex class II-bound peptide epitope (pMHCII). The enriched lymphocytes were subsequently quantified using fluorescence-activated cell sorting (FACS). This was the first use of magnetic nanowires for cell sorting using FACS, and improvements in both specificity and fluorescent signal strength were predicted due to higher particle moments and lengths than conventional paramagnetic beads. Three different types of nanowires (Ni, Fe with Au tip and Fe-Au multilayers) were made by electrodeposition. Ni nanowires separated fewer T cells than Au tipped Fe nanowires, likely because Ni has a lower magnetic moment than Fe. Fe-Au multilayer nanowires separated more T cells than Au-tipped Fe nanowires because there was more monomer per nanowire. Also, increasing the amount of monomer increased the number of CD4+ cells separated. Compared to conventional paramagnetic beads, the nanowires had lower specificity for CD4+ T cells, but had stronger fluorescent signals due to more fluorophores per particle. This results in broader FACS baseline separation between the positive and negative cells, which is useful to detect T cells, even those with lower binding affinity for pMHCII ligands.