bluuebunny/crossref_metadata_2025_split huggingface dataset:
The complex formed between a synthetic RNA aptamer and the transcription repressor TetR is a structural and functional twin of the operator DNA–TetR regulator complex
Authors: Grau Florian C , Jaeger Jeannine , Groher Florian , Suess Beatrix , Muller Yves A 
Published: February 2020

Abstract
RNAs play major roles in the regulation of gene expression. Hence, designer RNA molecules are increasingly explored as regulatory switches in synthetic biology. Among these, the TetR-binding RNA aptamer was selected by its ability to compete with operator DNA for binding to the bacterial repressor TetR. A fortuitous finding was that induction of TetR by tetracycline abolishes both RNA aptamer and operator DNA binding in TetR. This enabled numerous applications exploiting both the specificity of the RNA aptamer and the efficient gene repressor properties of TetR. Here, we present the crystal structure of the TetR-RNA aptamer complex at 2.7 Å resolution together with a comprehensive characterization of the TetR–RNA aptamer versus TetR–operator DNA interaction using site-directed mutagenesis, size exclusion chromatography, electrophoretic mobility shift assays and isothermal titration calorimetry. The fold of the RNA aptamer bears no resemblance to regular B-DNA, and neither does the thermodynamic characterization of the complex formation reaction. Nevertheless, the functional aptamer-binding epitope of TetR is fully contained within its DNA-binding epitope. In the RNA aptamer complex, TetR adopts the well-characterized DNA-binding-competent conformation of TetR, thus revealing how the synthetic TetR-binding aptamer strikes the chords of the bimodal allosteric behaviour of TetR to function as a synthetic regulator.
Microbiome Restoration by RBX2660 Does Not Preclude Recurrence of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report
Authors: Keen Eric C , Tasoff Preston , Hink Tiffany , Reske Kimberly A , Burnham Carey-Ann D , Dantas Gautam , Kwon Jennie H , Dubberke Erik R 
Published: February 2020

Abstract
A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.
A 72-Year-Old Female With Bow Hunter Syndrome: A Rare Surgical Approach to C4-5 Vertebral Artery Decompression: 2-Dimensional Operative Video
Authors: Gigliotti Michael J , Joseph Jacob , Thompson Byron Gregory , Park Paul 
Published: February 2020

Abstract
Bow hunter syndrome is defined as vertebrobasilar insufficiency due to mechanical occlusion of the vertebral artery during head and neck rotation. In many cases, this is due to osteophyte formation, disc herniation, cervical spondylosis, tendinous bands, or tumors. Symptomatic disease may vary from inducing transient vertigo to posterior circulation stroke. Although digital subtraction angiography is the gold standard in diagnosis, the underlying pathology in bow hunter syndrome may be detected with doppler ultrasound, computed tomography (CT) angiogram, magnetic resonance imaging and angiogram, and diagnostic angiography with dynamic testing. In this case, a 72-yr-old female with a recent right-sided cerebellar stroke underwent operative intervention to decompress the right vertebral artery at C4-C5 in order to relieve symptomatic bow hunter syndrome. Preoperative CT angiogram revealed bilateral significant stenosis of the vertebral arteries at the C4-C5 level with follow-up diagnostic angiogram revealing complete occlusion of the right vertebral artery with the head rotated right (compared to 80% occlusion observed when the patient's head was rotated left). Prior to the procedure, the patient experienced lightheadedness, diaphoresis, dizziness, and a sensation of facial flushing exacerbated by rotating her head to the right. To relieve her symptoms, operative intervention was undertaken. To access the lateral osteophytes originating from the uncovertebral joint, a C4-5 discectomy is utilized. The vertebral artery was decompressed, and a standard anterior cervical fusion was performed. Postoperatively, the patient was stable and was discharged 1 d after surgery. Postoperative imaging showed adequate decompression of the right vertebral artery at the level of C4-5.
The authors confirm that they have obtained, prior to submission, a written release from the patient authorizing use of this surgical video to be submitted and published in the journal Operative Neurosurgery, as well as consent to perform the procedure.
Genesis of Recent Mafic Magmatism in the Taupo Volcanic Zone, New Zealand: Insights into the Birth and Death of Very Large Volume Rhyolitic Systems?
Authors: Zellmer Georg F , Kimura Jun-Ichi , Stirling Claudine H , Lube Gert , Shane Phil A , Iizuka Yoshiyuki 
Published: February 2020

Abstract
Mafic magmatism of the rifting Taupo Volcanic Zone (TVZ) of the North Island, New Zealand, is volumetrically minor, but is thought to tap the material that provides the heat source for voluminous rhyolite production through partial melting of the crust, which ultimately results in very large volume explosive eruptions. We have studied the major and trace element chemistry of 14 mafic samples from across the entire TVZ, and the U isotopic composition of whole-rocks, groundmasses and separates of mafic mineral phases from a selection of nine samples (with the remaining five too sparsely phyric for mineral separation). Some minerals yield significant 234U enrichments despite groundmass and whole-rock close to 238U–234U secular equilibrium, pointing to uptake of variably hydrothermally altered antecrystic minerals prior to the eruption of originally sparsely phyric to aphyric mafic magmas. However, incompatible trace element patterns indicate that there are three chemically distinct groups of samples, and that samples may be used to derive primary melt compositions. We employ the latest version of the Arc Basalt Simulator (ABS5) to forward model these compositions, deriving mantle source parameters including mantle fertility, slab liquid flux, mantle volatile content, degree of melting, and P–T conditions of melt segregation. We show that mafic rocks erupted in areas of old, now inactive calderas constitute low-degree, deep melts, whereas those in areas of active caldera-volcanism are high-degree partial melts segregated from a less depleted source at an intermediate depth. Finally, high-Mg basaltic andesites erupted in the SW and NE of the TVZ point to a fertile, shallow mantle source. Our data are consistent with a petrogenetic model in which mantle melting is dominated by decompression, rather than fluid fluxing, and progresses from shallow to deeper levels with time. Melt volumes initially increase to a tipping point, at which large-scale crustal melting and caldera volcanism become prominent, and then decrease owing to progressive depletion of the mantle wedge by melting, resulting in the dearth of heat provided and eventual cessation of very large volume rhyolitic volcanism. ABS5 modelling therefore supports the notion of a direct link between the chemistry of recently erupted mafic magmas and the long-term activity and evolution of rhyolitic volcanism in the TVZ.
Metasomatism and Hydration of the Oceanic Lithosphere: a Case Study of Peridotite Xenoliths from Samoa
Authors: Ashley Aaron Wolfgang , Bizimis Michael , Peslier Anne H , Jackson Matthew , Konter Jasper G 
Published: February 2020

AbstractWater influences geodynamic processes such as melting, deformation and rheology, yet its distribution in the oceanic upper mantle is primarily known indirectly from melt inclusions and glasses of erupted mantle melts (i.e. mid-ocean ridge and ocean island basalts). To better constrain the mechanisms influencing the distribution of H2O in the mantle, particularly regarding the role of metasomatism, we analyzed 15 peridotite xenoliths from Savai‘i and two dunite xenoliths from Ta‘ū (Samoa) for structural H2O (by polarized Fourier transform infrared spectroscopy), and major and trace element concentrations. Clinopyroxenes from the Ta‘ū dunites show trace element concentrations consistent with equilibration with their host lavas, but lower H2O contents than expected. Savai‘i peridotites are highly depleted harzburgites (melt depletion ≥17 %). They show strong evidence of transient metasomatism by both carbonatite and silicate melts, with highly variable Ti and Zr depletions and light rare earth element enrichments. However, despite metasomatism the H2O concentrations in olivines (0 − 4 ppm H2O) and orthopyroxenes (17 − 89 ppm H2O) are among the lowest reported in oceanic xenoliths, but higher than expected for the estimated degree of depletion. In general, H2O concentrations vary less than those of other incompatible trace elements in these samples. Transects across mineral grains show generally homogeneous distributions of H2O, indicating no significant H2O loss or gain during ascent. Raman spectroscopy on inclusions in minerals shows the presence of CO2 but an absence of molecular H2O. This agrees with the absence of H2O concentration variations between inclusion-rich and -poor domains in minerals. The above data can be explained by transient metasomatism along grain boundaries, now recorded as planes of inclusions within annealed grains. Fast diffusion of hydrogen (but not lithophile elements) from the inclusions into the host mineral phase will simultaneously enrich H2O contents across the grain and lower them in the inclusion-rich domains. The result is highly variable metasomatism recorded in lithophile elements, with smaller magnitude H2O variations that are decoupled from lithophile element metasomatism. Comparison with xenoliths from Hawai‘i shows that evidence for metasomatism from lithophile elements alone does not imply rehydration of the oceanic lithosphere. Instead, H2O concentrations depend on the overall amount of H2O added to the lithosphere through metasomatism, and the proximity of sampled material to areas of melt infiltration in the lithosphere.
Smoking in spondyloarthritis: unravelling the complexities
Authors: Zhao Sizheng Steven , Goodson Nicola J , Robertson Selina , Gaffney Karl 
Published: February 2020

AbstractTobacco smoking is a major threat to health. There is no doubt about the need to promote and support cessation at every opportunity. Smoking has a clear role in RA, but what evidence is there that the same relationship exists in SpA? In this review, we examine (the less cited) paradoxes and contradictions in the existing axial SpA (axSpA) and PsA literature; for example, smoking appears to be ‘protective’ for some axSpA manifestations. We also highlight findings from higher quality evidence: smoking is associated with increased risk of PsA and the risk of psoriasis in axSpA. The relationship between smoking and SpA is far from simple. Our aim is to highlight the harms of smoking in SpA and bring attention to inconsistencies in the literature to inform further research.
Metabolism and Effects on Endogenous Metabolism of Paracetamol (Acetaminophen) in a Porcine Model of Liver Failure
Authors: Dargue Rebecca , Zia Rabiya , Lau Chungho , Nicholls Andrew W , Dare Theo O , Lee Karla , Jalan Rajiv , Coen Muireann , Wilson Ian D 
Published: February 2020

Abstract
The metabolic fate, toxicity, and effects on endogenous metabolism of paracetamol (acetaminophen, APAP) in 22 female Landrace cross large white pigs were evaluated in a model of acute liver failure (ALF). Anesthetized pigs were initially dosed at 250 mg/kg via an oroduodenal tube with APAP serum concentrations maintained above 300 mg/l using maintenance doses of 0.5–4 g/h until ALF. Studies were undertaken to determine both the metabolic fate of APAP and its effects on the endogenous metabolic phenotype of ALF in using 1H NMR spectroscopy. Increased concentrations of citrate combined with pre-ALF increases in circulating lactate, pyruvate, and alanine in plasma suggest mitochondrial dysfunction and a switch in hepatic energy metabolism to glycolysis in response to APAP treatment. A specific liquid chromatography-tandem mass spectrometry assay was used to quantify APAP and metabolites. The major circulating and urinary metabolite of APAP was the phenolic glucuronide (APAP-G), followed by p-aminophenol glucuronide (PAP-G) formed from N-deacetylated APAP. The PAP produced by N-deacetylation was the likely cause of the methemoglobinemia and kidney toxicity observed in this, and previous, studies in the pig. The phenolic sulfate of APAP, and the glutathione-derived metabolites of the drug were only found as minor components (with the cysteinyl conjugate detected but not the mercapturate). Given its low sulfation, combined with significant capacity for N-deacetylation the pig may represent a poor translational model for toxicology studies for compounds undergoing significant metabolism by sulfation, or which contain amide bonds which when hydrolyzed to unmask an aniline lead to toxicity. However, the pig may provide a useful model where extensive amide hydrolysis is seen for drugs or environmental chemicals in humans, but not in, eg, the rat and dog which are the preclinical species normally employed for safety assessment.
Anti-cancer Drug Synergy Prediction in Understudied Tissues using Transfer Learning
Authors: Kim Yejin , Zheng Shuyu , Tang Jing , Zheng W. Jim , Li Zhao , Jiang Xiaoqian 
Published: February 2020

AbstractMotivationExploring an exponentially increasing yet more promising space, high-throughput combinatorial drug screening has advantages in identifying cancer treatment options with higher efficacy without degradation in terms of safety. A key challenge is that accumulated number of observations in in-vitro drug responses varies greatly among different cancer types, where some tissues (such as bone and prostate) are understudied than the others. Thus, we aim to develop a drug synergy prediction model for understudied data-poor tissues as overcoming data scarcity problem.ResultsWe collected a comprehensive set of genetic, molecular, phenotypic features for cancer cell lines from six different databases. We developed a drug synergy prediction model based on deep neural networks to integrate multi-modal input and utilize transfer learning from data-rich tissues to data-poor tissues. We showed improved accuracy in predicting drug synergy in understudied tissues without enough drug combination screening data nor after-treatment transcriptome. Our synergy prediction model can be used to rank synergistic drug combinations in understudied tissues and thus help prioritizing future in-vitro experiments.Availability and ImplementationOur algorithm will be publicly available viahttps://github.com/yejinjkim/drug-synergy-prediction
Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group
Authors: Gorbalenya Alexander E. , Baker Susan C. , Baric Ralph S. , de Groot Raoul J. , Drosten Christian , Gulyaeva Anastasia A. , Haagmans Bart L. , Lauber Chris , Leontovich Andrey M , Neuman Benjamin W. , Penzar Dmitry , Perlman Stanley , Poon Leo L.M. , Samborskiy Dmitry , Sidorov Igor A. , Sola Isabel , Ziebuhr John 
Published: February 2020

AbstractThe present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of theCoronaviridaefamily, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the speciesSevere acute respiratory syndrome-related coronavirusand designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
Eicosanoid Inflammatory Mediators Are Robustly Associated with Blood Pressure in the General Population
Authors: Palmu Joonatan , Watrous Jeramie D. , Mercader Kysha , Havulinna Aki S. , Lagerborg Kim A. , Salosensaari Aaro , Inouye Mike , Larson Martin G. , Rong Jian , Vasan Ramachandran S. , Lahti Leo , Andres Allen , Cheng Susan , Jousilahti Pekka , Salomaa Veikko , Jain Mohit , Niiranen Teemu J. 
Published: February 2020

AbstractEpidemiological and animal studies have associated systemic inflammation with blood pressure (BP). However, the mechanistic factors linking inflammation and BP remain unknown. Fatty acid derived eicosanoids serve as mediators of inflammation and have been suggested to also regulate renal vascular tone, peripheral resistance, renin-angiotensin system, and endothelial function. We therefore hypothesize that specific pro- and anti-inflammatory eicosanoids are linked with BP. We studied a population sample of 8099 FINRISK 2002 participants randomly drawn from the Finnish population register (53% women, mean age 48±13 years) and, for external validation, a sample of 2859 Framingham Heart Study (FHS) Offspring study participants (55% women, mean age 66±9 years). Using non-targeted liquid chromatography-mass spectrometry, we profiled 545 distinct high-quality eicosanoids and related oxylipin mediators in plasma. Adjusting for conventional hypertension risk factors, we observed 187 (34%) metabolites that were significantly associated with systolic BP (P < Bonferroni-corrected threshold of 0.05/545). We used forward selection linear regression modeling in FINRISK to define a general formula for individual eicosanoid risk score. Individuals of the top risk score quartile in FINRISK had a 9.0 mmHg (95% CI 8.0-10.1) higher systolic BP compared with individuals in the lowest quartile in fully adjusted models. Observed metabolite associations were consistent across FINRISK and FHS. In conclusion, plasma eicosanoids demonstrate strong associations with BP in the general population. As eicosanoid compounds affect numerous physiological processes that are central to BP regulation, they may offer new insights regarding pathogenesis of hypertension, as well as serve as potential targets for therapeutic intervention.
The parotid secretory protein BPIFA2 is a salivary surfactant that affects LPS action
Authors: Nandula Seshagiri R. , Huxford Ian , Wheeler Thomas T. , Aparicio Conrado , Gorr Sven-Ulrik 
Published: February 2020

AbstractSaliva plays important roles in the mastication, swallowing and digestion of food, speech and lubrication of oral mucosa, antimicrobial and anti-inflammatory activity and control of body temperature in grooming animals. The salivary protein BPIFA2 (BPI fold containing family A member 2; former names: Parotid Secretory Protein, PSP, SPLUNC2, C20orf70) is related to lipid-binding and LPS-binding proteins expressed in mucosa. Indeed, BPIFA2 binds LPS but the physiological role of BPIFA2 remains to be determined. To address this question,Bpifa2knockout (Bpifa2tm1(KOMP)Vlcg) (KO) mice were phenotyped with a special emphasis on saliva and salivary glands. Saliva collected from KO mice was less able to spread on a hydrophobic surface than wild-type saliva and the surface tension of KO saliva was close to that of water. These data suggest that BPIFA2 is a salivary surfactant that is mainly responsible for the low surface tension of mouse saliva. The reduced surfactant activity of KO saliva did not affect consumption of dry food or grooming, but saliva from KO mice contained less LPS than wild-type saliva. Indeed, mice lacking BPIFA2 responded to ingested LPS with an increased stool frequency, suggesting that BPIFA2 plays a role in the solubilization and activity of ingested LPS. Consistent with these findings, BPIFA2-depleted mice also showed increased insulin secretion and metabolomic changes that were consistent with a mild endotoxemia. These results support the distal physiological function of a salivary protein and reinforce the connection between oral biology and systemic disease.
Rapid Prototyping of Wireframe Scaffolded DNA Origami using ATHENA
Authors: Jun Hyungmin , Wang Xiao , Bricker William P. , Jackson Steve , Bathe Mark 
Published: February 2020

ABSTRACTWireframe DNA origami assemblies can now be programmed automatically from the “top-down” using simple wireframe target geometries, or meshes, in 2D and 3D geometries using either rigid, six-helix bundle (6HB) or more compliant, two-helix bundle (2HB or DX) edges. While these assemblies have numerous applications in nanoscale materials fabrication due to their nanoscale spatial addressability and high degree of customization, no easy-to-use graphical user interface software yet exists to deploy these algorithmic approaches within a single, stand-alone interface. Here, we present ATHENA, an open-source software package with a graphical user interface that automatically renders single-stranded DNA scaffold routing and staple strand sequences for any target wireframe DNA origami in 2D or 3D using 2HB or 6HB edges. ATHENA enables external editing of sequences using the popular tool caDNAno, demonstrated here using asymmetric nanoscale positioning of gold nanoparticles, as well as atomic-level models for molecular dynamics, coarse-grained dynamics, or other computational chemistry simulation approaches. We anticipate ATHENA will significantly reduce the barrier for non-specialists to perform wireframe DNA origami sequence design and fabrication for custom applications in materials science, nanotechnology, therapeutics, and other areas.
Nyctinastic thallus movement in the liverwortMarchantia polymorphais regulated by a circadian clock
Authors: Lagercrantz Ulf , Billhardt Anja , Rousku Sabine N. , Eklund D. Magnus 
Published: February 2020

ABSTRACTThe circadian clock coordinates an organism’s growth, development and physiology with environmental factors. One illuminating example is the rhythmic growth of hypocotyls and cotyledons inArabidopsis thaliana. Such daily oscillations in leaf position are often referred to as sleep movements or nyctinasty. Here, we report that plantlets of the liverwortMarchantia polymorphashow analogous rhythmic movements of thallus lobes, and that the circadian clock controls this rhythm, with auxin a likely meditator. The mechanisms of this circadian clock are partly conserved as compared to angiosperms, with homologs to the core clock genesPRR,RVEandTOC1forming a core transcriptional feedback loop also inM. polymorpha.