bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA secondary structure prediction using an ensemble of two-dimensional deep neural networks and transfer learning
Authors: Singh Jaswinder , Hanson Jack , Paliwal Kuldip , Zhou Yaoqi 
Published: November 2019

AbstractThe majority of our human genome transcribes into noncoding RNAs with unknown structures and functions. Obtaining functional clues for noncoding RNAs requires accurate base-pairing or secondary-structure prediction. However, the performance of such predictions by current folding-based algorithms has been stagnated for more than a decade. Here, we propose the use of deep contextual learning for base-pair prediction including those noncanonical and non-nested (pseudoknot) base pairs stabilized by tertiary interactions. Since only$$<$$<250 nonredundant, high-resolution RNA structures are available for model training, we utilize transfer learning from a model initially trained with a recent high-quality bpRNA dataset of$$> $$>10,000 nonredundant RNAs made available through comparative analysis. The resulting method achieves large, statistically significant improvement in predicting all base pairs, noncanonical and non-nested base pairs in particular. The proposed method (SPOT-RNA), with a freely available server and standalone software, should be useful for improving RNA structure modeling, sequence alignment, and functional annotations.
Dual-energy X-ray absorptiometry-assessed adipose tissues in metabolically unhealthy normal weight Asians
Authors: Lu Yi-Chien , Lin Ying Chin , Yen Amy Ming-Fang , Chan Wing P. 
Published: November 2019

AbstractNormal body mass index (BMI) is associated with lower risk for cardiometabolic diseases. However, there is a subset of individuals with BMI in this range who present with this metabolic abnormality (called metabolically unhealthy normal weight, MUHNW). Here we aimed to assess the adipose characteristics of people with MUHNW using dual-energy X-ray absorptiometry (DXA). This study included 3259 people with normal BMI who underwent health examinations from January 1, 2007 through December 31, 2016. Body fat percentage (%BF), android-gynoid percent fat ratio (AG ratio), and visceral adipose tissue (VAT) were measured simultaneously using DXA CoreScan software. Those with MUHNW comprised 12.67% of the sample. Among those with MUHNW, 71.6% of the women and 56.5% of the men showed high VAT amounts, but less than 40% of either showed high %BFs. Furthermore, considering the combined effects of fat amount and distribution, a normal BMI accompanied by high AG ratio and/or high VAT mass but low %BF presents a much higher risk for metabolic syndrome than when %BF is high, most predominantly in women. In conclusion, using DXA-measured abdominal fat, particularly VAT accumulation, is clinically more important than using %BF when assessing metabolic syndrome in those with normal BMI.
Drivers of Microbial Carbon Fluxes Variability in Two Oligotrophic Mediterranean Coastal Systems
Authors: González-Benítez Natalia , García-Corral Lara S. , Morán Xosé Anxelu G. , Middelburg Jack J. , Pizay Marie Dominique , Gattuso Jean-Pierre 
Published: November 2019

AbstractThe carbon fluxes between phytoplankton and heterotrophic bacterioplankton were studied in two coastal oligotrophic sites in the NW Mediterranean. Phytoplankton and bacterial production rates were measured under natural conditions using different methods. In the Bay of Villefranche, the temporal variability revealed net heterotrophy in July-October and net autotrophy in December-March. The spatial variability was studied in the Bay of Palma, showing net autotrophic areas in the west and heterotrophic areas in the east. On average bacterial respiration, represented 62% of the total community respiration. Bacterial growth efficiency (BGE) values were significantly higher in autotrophic conditions than in heterotrophic ones. During autotrophic periods, dissolved primary production (DPP) was enough to sustained bacterial metabolism, although it showed a positive correlation with organic carbon stock (DOC). Under heterotrophic conditions, DPP did not sustain bacterial metabolism but bacterial respiration correlated with DPP and bacterial production with DOC. Temperature affected positively, DOC, BGE, bacterial respiration and production when the trophic status was autotrophic. To summarize, the response of bacterial metabolism to temperature and carbon sources depends on the trophic status within these oligotrophic coastal systems.
Platelet-derived- Extracellular Vesicles Promote Hemostasis and Prevent the Development of Hemorrhagic Shock
Authors: Lopez Ernesto , Srivastava Amit K. , Burchfield John , Wang Yao-Wei , Cardenas Jessica C. , Togarrati Padma Priya , Miyazawa Byron , Gonzalez Erika , Holcomb John B. , Pati Shibani , Wade Charles E. 
Published: November 2019

AbstractEvery year more than 500,000 deaths are attributed to trauma worldwide and severe hemorrhage is present in most of them. Transfused platelets have been shown to improve survival in trauma patients, although its mechanism is only partially known. Platelet derived-extracellular vesicles (PEVs) are small vesicles released from platelets upon activation and/or mechanical stimulation and many of the benefits attributed to platelets could be mediated through PEVs. Based on the available literature, we hypothesized that transfusion of human PEVs would promote hemostasis, reduce blood loss and attenuate the progression to hemorrhagic shock following severe trauma. In this study, platelet units from four different donors were centrifuged to separate platelets and PEVs. The pellets were washed to obtain plasma-free platelets to use in the rodent model. The supernatant was subjected to tangential flow filtration for isolation and purification of PEVs. PEVs were assessed by total count and particle size distribution by Nanoparticle Tracking Analysis (NTA) and characterized for cells of origin and expression of EV specific-surface and cytosolic markers by flow cytometry. The coagulation profile from PEVs was assessed by calibrated automated thrombography (CAT) and thromboelastography (TEG). A rat model of uncontrolled hemorrhage was used to compare the therapeutic effects of 8.7 × 108 fresh platelets (FPLT group, n = 8), 7.8 × 109 PEVs (PEV group, n = 8) or Vehicle (Control, n = 16) following severe trauma. The obtained pool of PEVs from 4 donors had a mean size of 101 ± 47 nm and expressed the platelet-specific surface marker CD41 and the EV specific markers CD9, CD61, CD63, CD81 and HSP90. All PEV isolates demonstrated a dose-dependent increase in the rate and amount of thrombin generated and overall clot strength. In vivo experiments demonstrated a 24% reduction in abdominal blood loss following liver trauma in the PEVs group when compared with the control group (9.9 ± 0.4 vs. 7.5 ± 0.5 mL, p < 0.001>). The PEV group also exhibited improved outcomes in blood pressure, lactate level, base excess and plasma protein concentration compared to the Control group. Fresh platelets failed to improve these endpoints when compared to Controls. Altogether, these results indicate that human PEVs provide pro-hemostatic support following uncontrolled bleeding. As an additional therapeutic effect, PEVs improve the outcome following severe trauma by maintaining hemodynamic stability and attenuating the development of ischemia, base deficit, and cardiovascular shock.
A comparative metabolomics analysis of the components of heartwood and sapwood in Taxus chinensis (Pilger) Rehd.
Authors: Shao Fenjuan , Zhang Lisha , Guo Juan , Liu Xiaochun , Ma Wenhui , Wilson Iain W. , Qiu Deyou 
Published: November 2019

AbstractTaxus chinensis is a well-known gymnosperm with great ornamental and medicinal value. Its purple red brown heartwood (HW) has many attributes such as straight texture, high density, mechanical strength, rich elasticity and corrosion resistance that is highly prized commercially. T. chinensis sapwood (SW), in comparison, lacks these important traits. At present, little is known about the differences of metabolites between the SW and HW in T. chinensis. Widely targeted metabolic profiling was performed to analyze the metabolic profiles of HW and SW in T. chinensis using Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-EI-MS). A total of 607 metabolites were detected in HW and SW. Among them, 146 metabolites were significantly higher, and 167 metabolites significantly lower, in HW as compared to SW. These differential metabolites were mainly involved in metabolic pathways and biosynthesis of secondary metabolites, such as flavonoids, flavone and flavonol, phenylpropanoids and antibiotics. Moreover, 71 flavonoids and isoflavones were found to be significantly different between HW and SW. Our results show the difference of components between the HW and SW, which has potential significance to further elucidate the mechanism of HW color formation. The results will provide insight into the metabolites associated with wood color formation and useful information for understanding the metabolites associated with wood quality.
Spin liquid mediated RKKY interaction
Authors: Legg Henry F. , Braunecker Bernd 
Published: November 2019

AbstractWe propose an RKKY-type interaction that is mediated by a spin liquid. If a spin liquid exists such an interaction could leave a fingerprint by ordering underlying localised moments such as nuclear spins. This interaction has a unique phenomenology that is distinct from the RKKY interaction found in fermionic systems; most notably the lack of a Fermi surface and absence of the requirement for itinerant electrons, since most spin liquids are insulators. We demonstrate that the interaction is predominately shaped by the lattice symmetries of the underlying spin liquid. As a working example we investigate the possible ordering of nuclear spins that interact through an underlying lattice of the two-dimensional spin-1/2 kagome antiferromagnet (KHAF), although the treatment remains general and can be extended to other spin liquids and dimensions. We find that several different nuclear spin orderings minimise the RKKY-type energy induced by the KHAF but are unstable due to a zero-energy flat magnon band in linear spin-wave theory. Despite this we show that a small magnetic field is able to gap out this magnon spectrum resulting in an intricate nuclear magnetism.
β-Cyclodextrin counteracts obesity in Western diet-fed mice but elicits a nephrotoxic effect
Authors: Scantlebery Angelique M. L. , Ochodnicky Peter , Kors Lotte , Rampanelli Elena , Butter Loes M. , El Boumashouli Chaima , Claessen Nike , Teske Gwen J. , van den Bergh Weerman Marius A. , Leemans Jaklien C. , Roelofs Joris J. T. H. , Florquin Sandrine 
Published: November 2019

AbstractObesity has become a worldwide health crisis and is associated with a plethora of comorbidities. The multi-organ effects of obesity have been linked to ectopic lipid accumulation. Thus, there is an urgent need to tackle the obesity crisis by developing effective lipid-lowering therapies. 2-hydroxypropyl-β-Cyclodextrin (2HP-β-CD) has been previously shown to reduce lysosomal cholesterol accumulation in a murine model of Niemann Pick Type C (NPC) disease. Using a murine model of Western diet-induced obesity (DIO), we report the effects of 2HP-β-CD in counteracting weight gain, expansion of adipose tissue mass and ectopic lipid accumulation. Interestingly, DIO caused intracellular storage of neutral lipids in hepatic tissues and of phospholipids in kidneys, both of which were prevented by 2HP-β-CD. Importantly, this report brings attention to the nephrotoxic effects of 2HP-β-CD: renal tubular damage, inflammation and fibrosis. These effects may be overlooked, as they are best appreciated upon assessment of renal histology.
Quantification of phosphoinositides reveals strong enrichment of PIP2 in HIV-1 compared to producer cell membranes
Authors: Mücksch Frauke , Citir Mevlut , Lüchtenborg Christian , Glass Bärbel , Traynor-Kaplan Alexis , Schultz Carsten , Brügger Britta , Kräusslich Hans-Georg 
Published: November 2019

AbstractHuman immunodeficiency virus type 1 (HIV-1) acquires its lipid envelope during budding from the plasma membrane of the host cell. Various studies indicated that HIV-1 membranes differ from producer cell plasma membranes, suggesting budding from specialized membrane microdomains. The phosphoinositide PI(4,5)P2 has been of particular interest since PI(4,5)P2 is needed to recruit the viral structural polyprotein Gag to the plasma membrane and thus facilitates viral morphogenesis. While there is evidence for an enrichment of PIP2 in HIV-1, fully quantitative analysis of all phosphoinositides remains technically challenging and therefore has not been reported, yet. Here, we present a comprehensive analysis of the lipid content of HIV-1 and of plasma membranes from infected and non-infected producer cells, resulting in a total of 478 quantified lipid compounds, including molecular species distribution of 25 different lipid classes. Quantitative analyses of phosphoinositides revealed strong enrichment of PIP2, but also of PIP3, in the viral compared to the producer cell plasma membrane. We calculated an average of ca. 8,000 PIP2 molecules per HIV-1 particle, three times more than Gag. We speculate that the high density of PIP2 at the HIV-1 assembly site is mediated by transient interactions with viral Gag polyproteins, facilitating PIP2 concentration in this microdomain. These results are consistent with our previous observation that PIP2 is not only required for recruiting, but also for stably maintaining Gag at the plasma membrane. We believe that this quantitative analysis of the molecular anatomy of the HIV-1 lipid envelope may serve as standard reference for future investigations.
Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron
Authors: Dipuglia Andrew , Cameron Matthew , Davis Jeremy A. , Cornelius Iwan M. , Stevenson Andrew W. , Rosenfeld Anatoly B. , Petasecca Marco , Corde Stéphanie , Guatelli Susanna , Lerch Michael L. F. 
Published: November 2019

AbstractMicrobeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron. We have developed the model for use as an independent verification tool for experiments in one of three MRT delivery rooms and therefore compare simulation results with equivalent experimental data. The normalised x-ray spectra produced by the Geant4 model and a previously validated analytical model, SPEC, showed very good agreement using wiggler magnetic field strengths of 2 and 3 T. However, the validity of absolute photon flux at the plane of the Phase Space File (PSF) for a fixed number of simulated electrons was unable to be established. This work shows a possible limitation of the G4SynchrotronRadiation process to model synchrotron radiation when using a variable magnetic field. To account for this limitation, experimentally derived normalisation factors for each wiggler field strength determined under reference conditions were implemented. Experimentally measured broadbeam and microbeam dose distributions within a Gammex RMI457 Solid Water® phantom were compared to simulated distributions generated by the Geant4 model. Simulated and measured broadbeam dose distributions agreed within 3% for all investigated configurations and measured depths. Agreement between the simulated and measured microbeam dose distributions agreed within 5% for all investigated configurations and measured depths.
Using the Sonification for Hardly Detectable Details in Medical Images
Authors: Chiroiu Veturia , Munteanu Ligia , Ioan Rodica , Dragne Ciprian , Majercsik Luciana 
Published: November 2019

AbstractThe inverse sonification problem is investigated in this article in order to detect hardly capturing details in a medical image. The direct problem consists in converting the image data into sound signals by a transformation which involves three steps - data, acoustics parameters and sound representations. The inverse problem is reversing back the sound signals into image data. By using the known sonification operator, the inverse approach does not bring any gain in the sonified medical imaging. The replication of the image already known does not help the diagnosis and surgical operation. In order to bring gains in the medical imaging, a new sonification operator is advanced in this paper, by using the Burgers equation of sound propagation. The sonified medical imaging is useful in interpreting the medical imaging that, however powerful they may be, are never good enough to aid tumour surgery. The inverse approach is exercised on several medical images used to surgical operations.
Projected slow down of South Indian Ocean circulation
Authors: Stellema Annette , Sen Gupta Alex , Taschetto Andréa S. 
Published: November 2019

AbstractUsing an ensemble of 28 climate models, we examine hindcasts and ‘business as usual’ future changes to large-scale South Indian Ocean dynamics. We compare model ensemble seasonal-to-annual volume transports to observations and explore drivers of past and future circulation variability and change. Off the west coast of Australia, models consistently project a weakening of the Leeuwin Current and Undercurrent due to reduced onshore flow and downwelling. The reduced onshore flow is related to changes in the alongshore pressure gradient. While the alongshore pressure gradient change is consistent with the Indonesian Throughflow projected weakening, we found no inter-model relationship between these changes. In the south-western Indian Ocean, the models project a robust weakening of the North East and South East Madagascar Currents, Agulhas Current and transport through the Mozambique Channel. This reduced Indian Ocean western boundary flow is partly associated with a weaker Indonesian Throughflow and overturning circulation, where the latter is related to a decrease in the convergence of deep Southern Ocean waters into the Indian Ocean. In contrast to the weakening of other features, the westward flowing Agulhas Current extension south of Africa is projected to strengthen, which is consistent with an intensification of the Antarctic Circumpolar Current.
Lineage tracing reveals the hierarchical relationship between neural stem cell populations in the mouse forebrain
Authors: Sachewsky Nadia , Xu Wenjun , Fuehrmann Tobias , van der Kooy Derek , Morshead Cindi M. 
Published: November 2019

AbstractSince the original isolation of neural stem cells (NSCs) in the adult mammalian brain, further work has revealed a heterogeneity in the NSC pool. Our previous work characterized a distinct, Oct4 expressing, NSC population in the periventricular region, through development and into adulthood. We hypothesized that this population is upstream in lineage to the more abundant, well documented, GFAP expressing NSC. Herein, we show that Oct4 expressing NSCs give rise to neurons, astrocytes and oligodendrocytes throughout the developing brain. Further, transgenic inducible mouse models demonstrate that the rare Oct4 expressing NSCs undergo asymmetric divisions to give rise to GFAP expressing NSCs in naïve and injured brains. This lineage relationship between distinct NSC pools contributes significantly to an understanding of neural development, the NSC lineage in vivo and has implications for neural repair.
Craniosynostosis surgery: workflow based on virtual surgical planning, intraoperative navigation and 3D printed patient-specific guides and templates
Authors: García-Mato David , Ochandiano Santiago , García-Sevilla Mónica , Navarro-Cuéllar Carlos , Darriba-Allés Juan V. , García-Leal Roberto , Calvo-Haro José A. , Pérez-Mañanes Rubén , Salmerón José I. , Pascau Javier 
Published: November 2019

AbstractCraniosynostosis must often be corrected using surgery, by which the affected bone tissue is remodeled. Nowadays, surgical reconstruction relies mostly on the subjective judgement of the surgeon to best restore normal skull shape, since remodeled bone is manually placed and fixed. Slight variations can compromise the cosmetic outcome. The objective of this study was to describe and evaluate a novel workflow for patient-specific correction of craniosynostosis based on intraoperative navigation and 3D printing. The workflow was followed in five patients with craniosynostosis. Virtual surgical planning was performed, and patient-specific cutting guides and templates were designed and manufactured. These guides and templates were used to control osteotomies and bone remodeling. An intraoperative navigation system based on optical tracking made it possible to follow preoperative virtual planning in the operating room through real-time positioning and 3D visualization. Navigation accuracy was estimated using intraoperative surface scanning as the gold-standard. An average error of 0.62 mm and 0.64 mm was obtained in the remodeled frontal region and supraorbital bar, respectively. Intraoperative navigation is an accurate and reproducible technique for correction of craniosynostosis that enables optimal translation of the preoperative plan to the operating room.
Nanomolar-potency ‘co-potentiator’ therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants
Authors: Phuan Puay-Wah , Tan Joseph-Anthony , Rivera Amber A. , Zlock Lorna , Nielson Dennis W. , Finkbeiner Walter E. , Haggie Peter M. , Verkman Alan S. 
Published: November 2019

AbstractAvailable CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of ‘co-potentiators’ (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants. Herein, a screen of ~120,000 drug-like synthetic small molecules identified active co-potentiators of pyrazoloquinoline, piperidine-pyridoindole, tetrahydroquinoline and phenylazepine classes, with EC50 down to ~300 nM following initial structure-activity studies. Increased CFTR chloride conductance by up to 8-fold was observed when a co-potentiator (termed ‘Class II potentiator’) was used with a classical potentiator (‘Class I potentiator’) such as VX-770 or GLPG1837. To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models. Co-potentiator efficacy was found for CFTR missense, deletion and nonsense mutations in nucleotide binding domain-2 (NBD2), including W1282X, N1303K, c.3700A > G and Q1313X (with corrector for some mutations). In contrast, CFTR mutations G85E, R334W, R347P, V520F, R560T, A561E, M1101K and R1162X showed no co-potentiator activity, even with corrector. Co-potentiator efficacy was confirmed in primary human bronchial epithelial cell cultures generated from a N1303K homozygous CF subject. The Class II potentiators identified here may have clinical benefit for CF caused by mutations in the NBD2 domain of CFTR.