bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells
Authors: Ojo Evelyn O. , Sharma Ashish Arunkumar , Liu Ruifu , Moreton Stephen , Checkley-Luttge Mary-Ann , Gupta Kalpana , Lee Grace , Lee Dean A. , Otegbeye Folashade , Sekaly Rafick-Pierre , de Lima Marcos , Wald David N. 
Published: October 2019

AbstractNK cell adoptive therapy is a promising cancer therapeutic approach, but there are significant challenges that limiting its feasibility and clinical efficacy. One difficulty is the paucity of clinical grade manufacturing platforms to support the large scale expansion of highly active NK cells. We created an NK cell feeder cell line termed ‘NKF’ through overexpressing membrane bound IL-21 that is capable of inducing robust and sustained proliferation (>10,000-fold expansion at 5 weeks) of highly cytotoxic NK cells. The expanded NK cells exhibit increased cytotoxic function against a panel of blood cancer and solid tumor cells as compared to IL-2-activated non-expanded NK cells. The NKF-expanded NK cells also demonstrate efficacy in mouse models of human sarcoma and T cell leukemia. Mechanistic studies revealed that membrane-bound IL-21 leads to an activation of a STAT3/c-Myc pathway and increased NK cell metabolism with a shift towards aerobic glycolysis. The NKF feeder cell line is a promising new platform that enables the large scale proliferation of highly active NK cells in support of large scale third party NK cell clinical studies that have been recently intiatied. These results also provide mechanistic insights into how membrane-bound IL-21 regulates NK cell expansion.
Emergent dynamics of neuromorphic nanowire networks
Authors: Diaz-Alvarez Adrian , Higuchi Rintaro , Sanz-Leon Paula , Marcus Ido , Shingaya Yoshitaka , Stieg Adam Z. , Gimzewski James K. , Kuncic Zdenka , Nakayama Tomonobu 
Published: October 2019

AbstractNeuromorphic networks are formed by random self-assembly of silver nanowires. Silver nanowires are coated with a polymer layer after synthesis in which junctions between two nanowires act as resistive switches, often compared with neurosynapses. We analyze the role of single junction switching in the dynamical properties of the neuromorphic network. Network transitions to a high-conductance state under the application of a voltage bias higher than a threshold value. The stability and permanence of this state is studied by shifting the voltage bias in order to activate or deactivate the network. A model of the electrical network with atomic switches reproduces the relation between individual nanowire junctions switching events with current pathway formation or destruction. This relation is further manifested in changes in 1/f power-law scaling of the spectral distribution of current. The current fluctuations involved in this scaling shift are considered to arise from an essential equilibrium between formation, stochastic-mediated breakdown of individual nanowire-nanowire junctions and the onset of different current pathways that optimize power dissipation. This emergent dynamics shown by polymer-coated Ag nanowire networks places this system in the class of optimal transport networks, from which new fundamental parallels with neural dynamics and natural computing problem-solving can be drawn.
Strategies to reduce genetic mosaicism following CRISPR-mediated genome edition in bovine embryos
Authors: Lamas-Toranzo I. , Galiano-Cogolludo B. , Cornudella-Ardiaca F. , Cobos-Figueroa J. , Ousinde O. , Bermejo-Álvarez P. 
Published: October 2019

AbstractGenetic mosaicism is the presence of more than two alleles on an individual and it is commonly observed following CRISPR microinjection of zygotes. This phenomenon appears when DNA replication precedes CRISPR-mediated genome edition and it is undesirable because it reduces greatly the odds for direct KO generation by randomly generated indels. In this study, we have developed alternative protocols to reduce mosaicism rates following CRISPR-mediated genome edition in bovine. In a preliminary study we observed by EdU incorporation that DNA replication has already occurred at the conventional microinjection time (20 hpi). Aiming to reduce mosaicism appearance, we have developed three alternative microinjection protocols: early zygote microinjection (10 hpi RNA) or oocyte microinjection before fertilization with either RNA or Ribonucleoprotein delivery (0 hpi RNA or 0 hpi RNP). All three alternative microinjection protocols resulted in similar blastocyst and genome edition rates compared to the conventional 20 hpi group, whereas mosaicism rates were significantly reduced in all early delivery groups (~10–30% of edited embryos being mosaic depending on the loci) compared to conventional 20 hpi microinjection (100% mosaicism rate). These strategies constitute an efficient way to reduce the number of indels, increasing the odds for direct KO generation.
Utility of High-Sensitivity and Conventional Troponin in Patients Undergoing Transcatheter Aortic Valve Replacement: Incremental Prognostic Value to B-type Natriuretic Peptide
Authors: Kobayashi Yukari , Kim Juyong B. , Moneghetti Kegan J. , Fischbein Michael , Lee Anson , Watkins Claire A. , Yeung Alan C. , Liang David , Ozen Mehmet O. , Demirci Utkan , Bowen Raffick , Fearon William F. , Haddad Francois 
Published: October 2019

AbstractHigh-sensitivity Troponin (hs-Tn) has emerged as a useful marker for patients with myocardial injury or heart failure. However, few studies have compared intermediate and hs-Tn in patients undergoing transcatheter aortic valve replacement (TAVR). Moreover, there remains uncertainty of which thresholds are the most useful for discriminating ventricular dysfunction or outcome. In this study we prospectively enrolled 105 patients with severe aortic stenosis (AS) who underwent TAVR as well as blood sampling for high-sensitivity (hs-TnI) and conventional troponin I (EXL-LOCI and RXL) assessment. Patients underwent comprehensive pre-procedure echocardiography. Ventricular dysfunction was defined using left ventricular mass index (LVMI), LV global longitudinal strain (LVGLS) and LV end-diastolic pressure. The mean age was 84.0 ± 8.7 years old and 60% were male sex with mean transaortic pressure gradient of 50.1 ± 16.0 mmHg and AVA of 0.63 ± 0.19 cm2. When using a threshold of 6 ng/L, 77% had positive hs-TnI while 27% had positive hs-TnI using recommended thresholds (16 ng/L for female and 34 ng/L for male). Troponin levels were higher in the presence of abnormal LV phenotypes. The strongest correlate of troponin was LVMI. During median follow-up of 375 days, 21 patients (20%) died. Lower threshold of hs-TnI and EXL-TnI was more discriminatory for overall mortality (Log-rank P = 0.03 for both), while higher threshold of hs-TnI (p = 0.75) and RXL-TnI were not (p = 0.30). Combining hs-TnI and BNP improved to predict long-term outcome (p = 0.004). In conclusion, hs-TnI levels correlated with the degree of LV dysfunction phenotypes. Furthermore, applying a lower threshold for hs-TnI performed better for outcome prediction than a recommended threshold in patients undergoing TAVR. Combining hs-TnI with BNP helped better risk stratification.
Long-term large-scale decline in relative abundances of butterfly and burnet moth species across south-western Germany
Authors: Habel Jan Christian , Trusch Robert , Schmitt Thomas , Ochse Michael , Ulrich Werner 
Published: October 2019

AbstractCurrent studies have shown a severe general decline in insect species diversity, their abundance, and a biomass reduction of flying insects. Most of previous studies have been performed at single sites, or were spatially restricted at the landscape level. In this study, we analyse trends of species richness and shifts in species composition of butterflies and burnet moth species across the federal state of Baden-Württemberg in south-western Germany, covering an area of 35,750 km2. The data set consists of 233,474 records and covers a period from 1750 until today. We grouped species according to their species´ specific functional traits and analyse how species with different habitat requirements and behaviour respond to land-use changes over time. Our data document a significant loss of relative abundance for most species, especially since the 1950s until today. Species demanding specific habitat requirements are more seriously suffering under this trend than generalists. This in particular affects taxa adapted to extensively used xerothermic grasslands, bogs or other habitats maintained by traditional low-productivity agricultural practices of the past. Our data indicate large-scale decline in relative abundance of many butterfly and burnet moth species, which happened in particular during the past few decades.
Transcriptome profiling of mouse samples using nanopore sequencing of cDNA and RNA molecules
Authors: Sessegolo Camille , Cruaud Corinne , Da Silva Corinne , Cologne Audric , Dubarry Marion , Derrien Thomas , Lacroix Vincent , Aury Jean-Marc 
Published: October 2019

AbstractOur vision of DNA transcription and splicing has changed dramatically with the introduction of short-read sequencing. These high-throughput sequencing technologies promised to unravel the complexity of any transcriptome. Generally gene expression levels are well-captured using these technologies, but there are still remaining caveats due to the limited read length and the fact that RNA molecules had to be reverse transcribed before sequencing. Oxford Nanopore Technologies has recently launched a portable sequencer which offers the possibility of sequencing long reads and most importantly RNA molecules. Here we generated a full mouse transcriptome from brain and liver using the Oxford Nanopore device. As a comparison, we sequenced RNA (RNA-Seq) and cDNA (cDNA-Seq) molecules using both long and short reads technologies and tested the TeloPrime preparation kit, dedicated to the enrichment of full-length transcripts. Using spike-in data, we confirmed that expression levels are efficiently captured by cDNA-Seq using short reads. More importantly, Oxford Nanopore RNA-Seq tends to be more efficient, while cDNA-Seq appears to be more biased. We further show that the cDNA library preparation of the Nanopore protocol induces read truncation for transcripts containing internal runs of T’s. This bias is marked for runs of at least 15 T’s, but is already detectable for runs of at least 9 T’s and therefore concerns more than 20% of expressed transcripts in mouse brain and liver. Finally, we outline that bioinformatics challenges remain ahead for quantifying at the transcript level, especially when reads are not full-length. Accurate quantification of repeat-associated genes such as processed pseudogenes also remains difficult, and we show that current mapping protocols which map reads to the genome largely over-estimate their expression, at the expense of their parent gene.
Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages
Authors: Sanchez Cristina L. , Sims Savannah G. , Nowery John D. , Meares Gordon P. 
Published: October 2019

AbstractIn many diseases, misfolded proteins accumulate within the endoplasmic reticulum (ER), leading to ER stress. In response, the cell initiates the unfolded protein response (UPR) to reestablish homeostasis. Additionally, in response to ER stress, various cell types mount an inflammatory response involving interleukin (IL)-6. While IL-6 has been widely studied, the impact of ER stress on other members of the IL-6 cytokine family, including oncostatin (OSM), IL-11, ciliary neurotrophic factor (CNTF), and leukemia inhibitor factor (LIF) remains to be elucidated. Here, we have examined the expression of the IL-6 family cytokines in response to pharmacologically-induced ER stress in astrocytes and macrophages, which express IL-6 in response to ER stress through different mechanisms. Our findings indicate that, in astrocytes, ER stress regulates mRNA expression of the IL-6 family of cytokines that is, in part, mediated by PKR-like ER kinase (PERK) and Janus kinase (JAK) 1. Additionally, in astrocytes, CNTF expression was suppressed through a PERK-dependent mechanism. Macrophages display a different profile of expression of the IL-6 family that is largely independent of PERK. However, IL-6 expression in macrophages was dependent on JAK signaling. Overall, this study demonstrates the cell-specific and differential mechanisms controlling expression of the IL-6 family of cytokines in response to ER stress.
Responses to depressive symptom items exhibit a common mathematical pattern across the European populations
Authors: Tomitaka Shinichiro , Kawasaki Yohei , Ide Kazuki , Akutagawa Maiko , Ono Yutaka , Furukawa Toshi A. 
Published: October 2019

AbstractThe theoretical distribution of responses to depressive symptom items in a general population remains unknown. Recent studies have shown that responses to depressive symptom items follow the same pattern in the US and Japanese populations, but the degree to which these findings can be generalized to other countries is unknown. The purpose of this study was to conduct a pattern analysis on the EU population’s responses to depressive symptom items using data from the Eurobarometer. The Eurobarometer questionnaires include six depressive symptom items from the 12-item General Health Questionnaire. The pattern analysis revealed that, across the entire EU population, the ratios between “score = 2” and “score = 1” and between “score = 3” to “score = 2” were similar among the six items and resulted in a common pattern. This common pattern was characterized by an intersection at a single point between “score = 0” and “score = 1” and a parallel pattern between “score = 1” and “score = 3” on a logarithmic scale. Country-by-country analyses revealed that the item responses followed a common characteristic pattern across all 15 countries. Our results suggest that responses to depressive symptom items in a general population follow the same characteristic pattern regardless of the specific country.
Reducing the ionizing radiation background does not significantly affect the evolution of Escherichia coli populations over 500 generations
Authors: Lampe Nathanael , Marin Pierre , Coulon Marianne , Micheau Pierre , Maigne Lydia , Sarramia David , Piquemal Fabrice , Incerti Sébastien , Biron David G. , Ghio Camille , Sime-Ngando Télesphore , Hindre Thomas , Breton Vincent 
Published: October 2019

AbstractOver millennia, life has been exposed to ionizing radiation from cosmic rays and natural radioisotopes. Biological experiments in underground laboratories have recently demonstrated that the contemporary terrestrial radiation background impacts the physiology of living organisms, yet the evolutionary consequences of this biological stress have not been investigated. Explaining the mechanisms that give rise to the results of underground biological experiments remains difficult, and it has been speculated that hereditary mechanisms may be involved. Here, we have used evolution experiments in standard and very low-radiation backgrounds to demonstrate that environmental ionizing radiation does not significantly impact the evolutionary trajectories of E. coli bacterial populations in a 500 generations evolution experiment.
Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel
Authors: Pasculli Barbara , Barbano Raffaela , Rendina Michelina , Fontana Andrea , Copetti Massimiliano , Mazza Tommaso , Valori Vanna Maria , Morritti Maria , Maiello Evaristo , Graziano Paolo , Murgo Roberto , Fazio Vito Michele , Esteller Manel , Parrella Paola 
Published: October 2019

AbstractMicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656–1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517–1.000) and 10-years (AUC: 0.804. 95%CI: 0.517–1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.
Loss of spatacsin impairs cholesterol trafficking and calcium homeostasis
Authors: Boutry Maxime , Pierga Alexandre , Matusiak Raphaël , Branchu Julien , Houllegatte Marc , Ibrahim Yoan , Balse Elise , El Hachimi Khalid-Hamid , Brice Alexis , Stevanin Giovanni , Darios Frédéric 
Published: October 2019

AbstractMutations in SPG11, leading to loss of spatacsin function, impair the formation of membrane tubules in lysosomes and cause lysosomal lipid accumulation. However, the full nature of lipids accumulating in lysosomes and the physiological consequences of such accumulation are unknown. Here we show that loss of spatacsin inhibits the formation of tubules on lysosomes and prevents the clearance of cholesterol from this subcellular compartment. Accumulation of cholesterol in lysosomes decreases cholesterol levels in the plasma membrane, enhancing the entry of extracellular calcium by store-operated calcium entry and increasing resting cytosolic calcium levels. Higher cytosolic calcium levels promote the nuclear translocation of the master regulator of lysosomes TFEB, preventing the formation of tubules and the clearance of cholesterol from lysosomes. Our work reveals a homeostatic balance between cholesterol trafficking and cytosolic calcium levels and shows that loss of spatacsin impairs this homeostatic equilibrium.
Unified and practical access to ɤ-alkynylated carbonyl derivatives via streamlined assembly at room temperature
Authors: Lv Xu-Lu , Shu Wei 
Published: October 2019

AbstractThe development of a unified and straightforward method for the synthesis of ɤ-alkynylated ketones, esters, and amides is an unmet challenge. Here we report a general and practical protocol to access ɤ-alkynylated esters, ketones, and amides with diverse substitution patterns enabled by dual-catalyzed spontaneous formation of Csp3–sp3 and Csp3–sp bond from alkenes at room temperature. This directing-group-free strategy is operationally simple, and allows for the straightforward introduction of an alkynyl group onto ɤ-position of carbonyl group along with the streamlined skeleton assembly, providing a unified protocol to synthesize various ɤ-alkynylated esters, acids, amides, ketones, and aldehydes, from readily available starting materials with excellent functional group compatibility.
The Contribution of Individual Differences in Memory Span and Language Ability to Spatial Release From Masking in Young Children
Authors: MacCutcheon Douglas , Pausch Florian , Füllgrabe Christian , Eccles Renata , van der Linde Jeannie , Panebianco Clorinda , Fels Janina , Ljung Robert 
Published: October 2019

Purpose
Working memory capacity and language ability modulate speech reception; however, the respective roles of peripheral and cognitive processing are unclear. The contribution of individual differences in these abilities to utilization of spatial cues when separating speech from informational and energetic masking backgrounds in children has not yet been determined. Therefore, this study explored whether speech reception in children is modulated by environmental factors, such as the type of background noise and spatial configuration of target and noise sources, and individual differences in the cognitive and linguistic abilities of listeners.

Method
Speech reception thresholds were assessed in 39 children aged 5–7 years in simulated school listening environments. Speech reception thresholds of target sentences spoken by an adult male consisting of number and color combinations were measured using an adaptive procedure, with speech-shaped white noise and single-talker backgrounds that were either collocated (target and back-ground at 0°) or spatially separated (target at 0°, background noise at 90° to the right). Spatial release from masking was assessed alongside memory span and expressive language.

Results and Conclusion
Significant main effect results showed that speech reception thresholds were highest for informational maskers and collocated conditions. Significant interactions indicated that individual differences in memory span and language ability were related to spatial release from masking advantages. Specifically, individual differences in memory span and language were related to the utilization of spatial cues in separated conditions. Language differences were related to auditory stream segregation abilities in collocated conditions that lack helpful spatial cues, pointing to the utilization of language processes to make up for losses in spatial information.
Estimating the economic potential of PV rooftop systems in South Africa's residential sector: a tale of eight metropolitan cities
Authors: Senatla Mamahloko , Bansal Ramesh C. , Naidoo Raj , Chiloane Lehlogonolo , Mudau Unarine 
Published: October 2019

The cost of producing electricity with solar photovoltaic (PV) has decreased drastically in the past 10 years, so much that the installed PV capacity has increased exponentially between 2010 and 2018. South Africa is endowed with a technical potential of 72 GW for PV rooftop systems, but the economic potential is largely unknown. As a result, the integrated resource plan assumes that an annual installation of 200 MW of distributed generation will be made between 2018 and 2030. This study evaluates the economic potential of rooftop PV systems in the residential sector within metropolitan cities in South Africa using financial metrics. The important financial metrics used to qualify an investment are net present value, internal rate of return (IRR) and payback period. An investment is expected to pay itself back in less than 10 years with a high rate of return (IRR). Households are classified into living standards measure so that it is easier to map customers to related tariffs. Using this method, the eight metropolitan municipalities will have PV economic potential of 11 GW in 2019 and 22.7 GW by 2030 if the current tariff grows at 5% and the tariff structure does not change.