bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts of Emissions of C2‐C5 Alkanes From the U.S. Oil and Gas Sector on Ozone and Other Secondary Species
Authors: Tzompa‐Sosa Z. A. , Fischer E. V. 
Published: May 2020

AbstractInside many U.S. oil and gas‐producing regions, the oil and gas sector dominates local anthropogenic emission fluxes of C2‐C5 alkanes. Here, we present a detailed analysis of the impact of these emissions on secondary species production over the continental United States using the GEOS‐Chem model. Oil‐ and gas‐producing areas in the central United States show the highest summertime surface ozone (O3) enhancements due to oil and gas C2‐C5 alkane emissions. The Colorado Front Range is the most impacted 8‐hr O3 non‐attainment area in the United States with 3‐hr daytime instantaneous O3 enhancements >4 ppb. From three selected non‐attainment areas, the Colorado Front Range has (1) the lowest monthly mean VOC reactivity (1.5 s−1); (2) the highest percent contribution of oil and gas sources (52%) to calculated VOC reactivity; and (3) the largest relative increases in PAN (peroxyacetyl nitrate), PPN (peroxypropionyl nitrate), and >C4 alkyl nitrates. Enhanced abundances of PAN, PPN, and >C4 alkyl nitrates have the potential to perturb remote O3 production through increased NOx export to remote regions via PAN chemistry. Globally, simulated C2‐C5 alkane emissions from the U.S. oil and gas sector contribute 0.5 Tg (~0.17%) to the tropospheric O3 burden with a ~0.27% contribution in the Northern Hemisphere.
A Late Miocene to Late Pleistocene Reconstruction of Precipitation Isotopes and Climate From Hydrated Volcanic Glass Shards and Biomarkers in Central Alaska and Yukon
Authors: Otiniano Gerard A. , Porter Trevor J. , Benowitz Jeff A. , Bindeman Ilya N. , Froese Duane G. , Jensen Britta J. L. , Davies Lauren J. , Phillips Michael A. 
Published: May 2020

AbstractThe Pliocene (5.3–2.6 Ma), an epoch with periods of climatic warmth and possible analogue for the future, has been well‐characterized globally by marine geochemical proxies. However, far less is known about Pliocene warmth at continental high latitudes, where the greatest impacts of warming are expected. This study seeks to better characterize the Pliocene climate of central Alaska and Yukon based on a reconstruction of the stable hydrogen isotope composition of precipitation relative to modern (ΔδDprecip) preserved in volcanic glass shards, a proxy for mean air temperature. The studied tephras are from a regional suite of outcrops that, when assembled into a composite record of ΔδDprecip, can be used to resolve broad trends during the late Miocene (6.7–5.86 Ma, n = 5), Pliocene (5.08–2.81 Ma, n = 7), and late Pleistocene (0.74–0.03 Ma, n = 3). These trends indicate that Pliocene ΔδDprecip estimates were generally more enriched in heavy isotopes than the latest Miocene, Pleistocene, and modern intervals. ΔδDprecip is likely influenced by changes in regional boundary conditions including orographic barriers, depositional environments, and ocean‐atmospheric circulation, but ΔδDprecip trends are most consistent with reconstructed temperatures from Yukon‐Alaska and North Pacific marine records. As such, this record appears predominantly sensitive to regional climate. Furthermore, qualitative temperature inferences from branched‐chain glycerol dialkyl glycerol tetraethers (brGDGTs) from four of our sites dating between 2.91 and 6.17 Ma corroborate elevated temperatures during the early Pliocene. Overall, this study demonstrates the viability of volcanic glass δD as a proxy for ΔδDprecip and late Cenozoic climate change in this region.
Electromagnetic Radial Diffusion in the Earth's Radiation Belts as Determined by the Solar Wind Immediate Time History and a Toy Model for the Electromagnetic Fields
Authors: Lejosne Solène 
Published: May 2020

AbstractDiffusion‐driven radiation belt models require multiple physics‐based inputs to specify the radiation environment through which spacecraft travel, including diffusion coefficients. Even though event‐specific coefficients are necessary for model accuracy, their routine integration in operational models has not yet been achieved. In fact, one of the key inputs, the radial diffusion coefficient, is still commonly determined by a Kp‐driven parameterization. This work presents a method to determine continuous time series of time‐varying radial diffusion coefficients. A theoretical model is developed in which electromagnetic radial diffusion is controlled by the magnetopause immediate time history. Specifically, radial diffusion is described as a function of the average, variance, and autocorrelation time of the geocentric standoff distance to the subsolar point on the magnetopause. Because the magnitudes of these three magnetopause parameters vary with time and magnetic activity, so does radial diffusion. To a lesser extent, radial diffusion is also controlled by the drift frequency of the radiation belt population. Moreover, radial diffusion is quantified using a standard model in which the magnetopause is controlled by the solar wind. Although the resulting diffusion coefficients span several orders of magnitude per Kp index, the median magnitudes are remarkably similar to the ones provided by the standard Kp‐driven statistical parameterization.
Therapeutic targeting of p300/CBP HAT domain for the treatment of NUT midline carcinoma
Authors: Zhang Xin , Zegar Tim , Lucas Anais , Morrison-Smith Chevaun , Knox Tatiana , French Christopher A. , Knapp Stefan , Müller Susanne , Siveke Jens T. 
Published: May 2020

AbstractNuclear protein of the testis (NUT) midline carcinoma (NMC), is a rare and highly aggressive form of undifferentiated squamous cell carcinoma. NMC is molecularly characterized by chromosomal rearrangement of theNUTgene to another gene, most commonly the bromodomain and extraterminal domain (BET) geneBRD4, forming theBRD4-NUTfusion oncogene. Therefore, inhibiting BRD4-NUT oncogenic function directly by BET inhibitors represents an attractive therapeutic approach but toxicity may limit the use of pan-BET inhibitors treating this cancer. We thus performed a drug screening approach using a library consisting of epigenetic compounds and ‘Donated Chemical Probes’ collated by the Structural Genomics Consortium (SGC) and identified the p300/CBP HAT inhibitor A-485, in addition to the well-known BET inhibitor JQ1, to be the most active candidate for NMC treatment. In contrast to JQ1, A-485 was selectively potent in NMC compared to other cell lines tested. Mechanistically, A-485 inhibited p300-mediated histone acetylation, leading to disruption of BRD4-NUT binding to hyperacetylated megadomains. Consistently, BRD4-NUT megadomain-associated genesMYC,CCAT1andTP63were downregulated by A-485. A-485 strongly induced squamous differentiation, cell cycle arrest and apoptosis. Combined inhibition of p300/CBP and BET showed synergistic effects. In summary, we identified the p300/CBP HAT domain as a putative therapeutic target in highly therapy-resistant NMC.
Telomere-based risk models for the early diagnosis of clinically significant prostate cancer
Authors: Rubio Galisteo Juan Manuel , Fernández Luis , Gómez Gómez Enrique , de Pedro Nuria , Cano Castiñeira Roque , Pedregosa Ana Blanca , Guler Ipek , Carrasco Valiente Julia , Esteban Laura , González Sheila , Castelló Nila , Otero Lissette , García Jorge , Segovia Enrique , Requena Tapia María José , Najarro Pilar 
Published: May 2020

Abstract
Background
The objective of this study was to explore telomere-associated variables (TAV) as complementary biomarkers in the early diagnosis of prostate cancer (PCa), analyzing their application in risk models for significant PCa (Gleason score > 6).

Methods
As part of a larger prospective longitudinal study of patients with suspicion of PCa undergoing prostate biopsy according to clinical practice, a subgroup of patients (n = 401) with PSA 3–10 ng/ml and no prior biopsies was used to evaluate the contribution of TAV to discern non-significant PCa from significant PCa. The cohort was randomly split for training (2/3) and validation (1/3) of the models. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate TAV in peripheral blood mononucleated cells. Models were generated following principal component analysis and random forest and their utility as risk predictors was evaluated by analyzing their predictive capacity and accuracy, summarized by ROC curves, and their clinical benefit with decision curves analysis.

Results
The median age of the patients was 63 years, with a median PSA of 5 ng/ml and a percentage of PCa diagnosis of 40.6% and significant PCa of 19.2%. Two TAV-based risk models were selected (TAV models 1 and 2) with an AUC ≥ 0.83 in the full study cohort, and AUC > 0.76 in the internal validation cohort. Both models showed an improvement in decision capacity when compared to the application of the PCPT-RC in the low-risk probabilities range. In the validation cohort, with TAV models 1 and 2, 33% /48% of biopsies would have been avoided losing 0/10.3% of significant PCa, respectively. The models were also tested and validated on an independent, retrospective, non contemporary cohort.

Conclusions
Telomere analysis through TAV should be considered as a new risk-score biomarker with potential to increase the prediction capacity of significant PCa in patients with PSA between 3–10 ng/ml.
Age influences structural brain restoration during weight gain therapy in anorexia nervosa
Authors: Kaufmann Lisa-Katrin , Hänggi Jürgen , Jäncke Lutz , Baur Volker , Piccirelli Marco , Kollias Spyros , Schnyder Ulrich , Martin-Soelch Chantal , Milos Gabriella 
Published: May 2020

AbstractNeuroimaging studies on anorexia nervosa (AN) have consistently reported globally reduced gray matter in patients with acute AN. While first studies on adolescent AN patients provide evidence for the reversibility of these impairments after weight gain, longitudinal studies with detailed regional analysis for adult AN patients are lacking and factors associated with brain restitution are poorly understood. We investigated structural changes in anorexia nervosa using T1-weighted magnetic resonance images with surface-based morphometry. The sample consisted of 26 adult women with severe AN and 30 healthy controls. The longitudinal design comprised three time points, capturing the course of weight-restoration therapy in AN patients at distinct stages of weight gain (BMI ≤ 15.5 kg/m2; 15.5 < BMI < 17.5 kg/m2; BMI ≥ 17.5 kg/m2). Compared to controls, AN patients showed globally decreased cortical thickness and subcortical volumes at baseline. Linear mixed effect models revealed the reversibility of these alterations, with brain restoration being most pronounced during the first half of treatment. The restoration of cortical thickness of AN patients negatively correlated with age, but not duration of illness. After weight restoration, residual group differences of cortical thickness remained in the superior frontal cortex. These findings indicate that structural brain alterations of adult patients with severe AN recuperate independently of the duration of illness during weight-restoration therapy. The temporal pattern of brain restoration suggests a decrease in restoration rate over the course of treatment, with patients’ age as a strong predictor of brain restitution, possibly reflecting decreases of brain plasticity as patients grow older.
Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies
Authors: Liu Peipei , McMenamin Úna C. , Johnston Brian T. , Murchie Peter , Iversen Lisa , Lee Amanda J. , Vissers Pauline A. J. , Cardwell Chris R. 
Published: May 2020

Abstract
Background
Studies have shown increased gastric cancer risk in users of proton pump inhibitors (PPI) and histamine-2 receptor antagonists, questioning the safety of gastric acid suppression. Therefore, we conducted a case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database and a cohort study in the UK Biobank.

Methods
In PCCIU, five controls were matched to cases diagnosed in 1999–2011, and medications were determined from GP records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. In the UK Biobank, medications were self-reported at cohort entry 2006–2010, and gastric cancer ascertained from cancer registries until 2014. Hazard ratios (HR) were calculated using Cox regression.

Results
PCCIU contained 1119 cases and 5394 controls. UK Biobank contained 250 cases in 471,779 participants. PPI users had a higher gastric cancer risk in PCCIU and UK Biobank when applying a 1-year lag (adjusted OR = 1.49, 95% CI 1.24, 1.80; adjusted HR = 1.28, 95% CI 0.86, 1.90, respectively), but these associations were attenuated when using a 2-year lag (adjusted OR = 1.13, 95% CI 0.91, 1.40; adjusted HR = 1.15, 95% CI 0.73, 1.82, respectively).

Conclusions
Overall, we observed little consistent evidence of an increased risk of gastric cancer with PPI use.
Histone deacetylase 1 and 2 drive differentiation and fusion of progenitor cells in human placental trophoblasts
Authors: Jaju Bhattad Gargi , Jeyarajah Mariyan J. , McGill Megan G. , Dumeaux Vanessa , Okae Hiroaki , Arima Takahiro , Lajoie Patrick , Bérubé Nathalie G. , Renaud Stephen J. 
Published: May 2020

AbstractCell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs by differentiation of underlying progenitor cells called cytotrophoblasts, which then fuse into the syncytiotrophoblast layer. Differentiation is associated with chromatin remodeling and specific changes in gene expression mediated, at least in part, by histone acetylation. However, the epigenetic regulation of human cytotrophoblast differentiation and fusion is poorly understood. In this study, we found that human syncytiotrophoblast development was associated with deacetylation of multiple core histone residues. Chromatin immunoprecipitation sequencing revealed chromosomal regions that exhibit dynamic alterations in histone H3 acetylation during differentiation. These include regions containing genes classically associated with cytotrophoblast differentiation (TEAD4,TP63,OVOL1,CGB), as well as near genes with novel regulatory roles in trophoblast development and function, such asLHX4andSYDE1. Prevention of histone deacetylation using both pharmacological and genetic approaches inhibited trophoblast fusion, supporting a critical role of this process for trophoblast differentiation. Finally, we identified the histone deacetylases (HDACs) HDAC1 and HDAC2 as the critical mediators driving cytotrophoblast differentiation. Collectively, these findings provide novel insights into the epigenetic mechanisms underlying trophoblast fusion during human placental development.
Apoptosome-dependent myotube formation involves activation of caspase-3 in differentiating myoblasts
Authors: H. Dehkordi Mahshid , Tashakor Amin , O’Connell Enda , Fearnhead Howard O. 
Published: May 2020

AbstractCaspase-2, -9, and -3 are reported to control myoblast differentiation into myotubes. This had been previously explained by phosphatidylserine exposure on apoptotic myoblasts inducing differentiation in neighboring cells. Here we show for the first time that caspase-3 is activated in the myoblasts undergoing differentiation. Using RNAi, we also demonstrate that differentiation requires both cytochrome c and Apaf-1, and by using a new pharmacological approach, we show that apoptosome formation is required. We also show that Bid, whose cleavage links caspase-2 to the mitochondrial death pathway, was required for differentiation, and that the caspase cleavage product, tBid, was generated during differentiation. Taken together, these data suggest that myoblast differentiation requires caspase-2 activation of the mitochondrial death pathway, and that this occurs in the cells that differentiate. Our data also reveal a hierarchy of caspases in differentiation with caspase-2 upstream of apoptosome activation, and exerting a more profound control of differentiation, while caspases downstream of the apoptosome primarily control cell fusion.
Monitoring for neovascular age-related macular degeneration (AMD) reactivation at home: the MONARCH study
Authors: Ward Elizabeth , Wickens Robin A. , O’Connell Abby , Culliford Lucy A. , Rogers Chris A. , Gidman Eleanor A. , Peto Tunde , Knox Paul C. , Burton Benjamin J. L. , Lotery Andrew J. , Sivaprasad Sobha , Donnelly Michael , Treanor Charlene , Hogg Ruth E. , Reeves Barnaby C. 
Published: May 2020

Abstract
Aims
This study aims to quantify the diagnostic test-accuracy of three visual function self-monitoring tests for detection of active disease in patients with neovascular age-related macular degeneration (nAMD) when compared with usual care. An integrated qualitative study will investigate the acceptability of these home-based testing strategies.

Methods
All consenting participants are provided with an equipment pack containing an iPod touch with two vision test applications installed and a paper journal of reading tests. Participants self-monitor their vision at home each week with all three tests for 12–18 months. Usual care continues over this period. Key eligibility criteria are: age ≥50 years; at least one eye with AMD with ≥6–≤42 months since first AMD treatment; and vision not worse than Snellen 6/60, LogMAR 1.04 or 33 letters. The primary outcome, and reference standard, is diagnosis of active disease during usual care monitoring in the Hospital Eye Service. Secondary outcomes include duration of study participation, ability of participants to do the tests, adherence to weekly testing and acceptability of the tests to participants.

Conclusions
Recruitment is in progress at five NHS centres. Challenges in procuring equipment, setting up the devices and transporting devices containing lithium batteries to participating sites delayed the start of recruitment. The study will describe the performance of the tests self-administered at home in detecting active disease compared to usual care monitoring. It will also describe the feasibility of the NHS implementing patient-administered electronic tests or similar applications at home for monitoring health.
Fast response of cold ice-rich permafrost in northeast Siberia to a warming climate
Authors: Nitzbon Jan , Westermann Sebastian , Langer Moritz , Martin Léo C. P. , Strauss Jens , Laboor Sebastian , Boike Julia 
Published: May 2020

AbstractThe ice- and organic-rich permafrost of the northeast Siberian Arctic lowlands (NESAL) has been projected to remain stable beyond 2100, even under pessimistic climate warming scenarios. However, the numerical models used for these projections lack processes which induce widespread landscape change termed thermokarst, precluding realistic simulation of permafrost thaw in such ice-rich terrain. Here, we consider thermokarst-inducing processes in a numerical model and show that substantial permafrost degradation, involving widespread landscape collapse, is projected for the NESAL under strong warming (RCP8.5), while thawing is moderated by stabilizing feedbacks under moderate warming (RCP4.5). We estimate that by 2100 thaw-affected carbon could be up to three-fold (twelve-fold) under RCP4.5 (RCP8.5), of what is projected if thermokarst-inducing processes are ignored. Our study provides progress towards robust assessments of the global permafrost carbon–climate feedback by Earth system models, and underlines the importance of mitigating climate change to limit its impacts on permafrost ecosystems.
Genomic landscape of platinum resistant and sensitive testicular cancers
Authors: Loveday Chey , Litchfield Kevin , Proszek Paula Z. , Cornish Alex J. , Santo Flavia , Levy Max , Macintyre Geoff , Holryod Amy , Broderick Peter , Dudakia Darshna , Benton Barbara , Bakir Maise Al , Hiley Crispin , Grist Emily , Swanton Charles , Huddart Robert , Powles Tom , Chowdhury Simon , Shipley Janet , O’Connor Simon , Brenton James D. , Reid Alison , de Castro David Gonzalez , Houlston Richard S. , Turnbull Clare 
Published: May 2020

AbstractWhile most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.
High-throughput cell and spheroid mechanics in virtual fluidic channels
Authors: Panhwar Muzaffar H. , Czerwinski Fabian , Dabbiru Venkata A. S. , Komaragiri Yesaswini , Fregin Bob , Biedenweg Doreen , Nestler Peter , Pires Ricardo H. , Otto Oliver 
Published: May 2020

AbstractMicrofluidics by soft lithography has proven to be of key importance for biophysics and life science research. While being based on replicating structures of a master mold using benchtop devices, design modifications are time consuming and require sophisticated cleanroom equipment. Here, we introduce virtual fluidic channels as a flexible and robust alternative to microfluidic devices made by soft lithography. Virtual channels are liquid-bound fluidic systems that can be created in glass cuvettes and tailored in three dimensions within seconds for rheological studies on a wide size range of biological samples. We demonstrate that the liquid-liquid interface imposes a hydrodynamic stress on confined samples, and the resulting strain can be used to calculate rheological parameters from simple linear models. In proof-of-principle experiments, we perform high-throughput rheology inside a flow cytometer cuvette and show the Young’s modulus of isolated cells exceeds the one of the corresponding tissue by one order of magnitude.
Olfactory marker protein directly buffers cAMP to avoid depolarization-induced silencing of olfactory receptor neurons
Authors: Nakashima Noriyuki , Nakashima Kie , Taura Akiko , Takaku-Nakashima Akiko , Ohmori Harunori , Takano Makoto 
Published: May 2020

AbstractOlfactory receptor neurons (ORNs) use odour-induced intracellular cAMP surge to gate cyclic nucleotide-gated nonselective cation (CNG) channels in cilia. Prolonged exposure to cAMP causes calmodulin-dependent feedback-adaptation of CNG channels and attenuates neural responses. On the other hand, the odour-source searching behaviour requires ORNs to be sensitive to odours when approaching targets. How ORNs accommodate these conflicting aspects of cAMP responses remains unknown. Here, we discover that olfactory marker protein (OMP) is a major cAMP buffer that maintains the sensitivity of ORNs. Upon the application of sensory stimuli, OMP directly captured and swiftly reduced freely available cAMP, which transiently uncoupled downstream CNG channel activity and prevented persistent depolarization. Under repetitive stimulation,OMP-/-ORNs were immediately silenced after burst firing due to sustained depolarization and inactivated firing machinery. Consequently,OMP-/-mice showed serious impairment in odour-source searching tasks. Therefore, cAMP buffering by OMP maintains the resilient firing of ORNs.