bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamical Drivers of the Local Wind Regime in a Himalayan Valley
Authors: Potter Emily R. , Orr Andrew , Willis Ian C. , Bannister Daniel , Salerno Franco 
Published: November 2018

AbstractUnderstanding the local valley wind regimes in the Hindu‐Kush Karakoram Himalaya is vital for future predictions of the glacio‐hydro‐meteorological system. Here the Weather Research and Forecasting model is employed at a resolution of 1 km to investigate the forces driving the local valley wind regime in a river basin in the Nepalese Himalaya, during July 2013 and January 2014. Comparing with observations shows that the model represents the diurnal cycle of the winds well, with strong daytime up‐valley winds and weak nighttime winds in both months. A momentum budget analysis of the model output shows that in the summer run the physical drivers of the near‐surface valley wind also have a clear diurnal cycle, and are dominated by the pressure gradient, advection, and turbulent vertical mixing, as well as a nonphysical numerical diffusion term. By contrast, the drivers in the winter run have a less consistent diurnal cycle. In both months, the pressure gradient, advection, numerical diffusion, and Coriolis terms dominate up to 5,000 m above the ground. The drivers are extremely variable over the valley, and also influenced by the presence of glaciers. When glaciers are removed from the model in the summer run, the wind continues further up the valley, indicating how the local valley winds might respond to future glacier shrinkage. The spatial variability of the drivers over both months is consistent with the complex topography in the basin, which must therefore be well represented in weather and regional climate models to generate accurate outputs.
Generalised muscle weakness after bladder wall injection of Abobotulinum Toxin A: experience of a woman with tetraplegia who required increased caregiver support: importance of doctor–patient communication: duty of candour for spinal cord physician and responsibilities of a patient
Authors: Vaidyanathan Subramanian , Foster Tracey , Soni Bakul M. 
Published: November 2018

Abstract
Introduction
Generalised muscle weakness can occur after bladder wall injection of Abobotulinum toxin and the patient may require additional caregiver support.

Case presentation
A woman with C-8 AIS A tetraplegia received bladder wall injection of Abobotulinum toxin A 1000 units for detrusor over-activity. After 2.5 weeks, she developed weakness of arms; could not lift herself for pressure relief; could not transfer using sliding board; she regained the original muscle strength in 6 weeks. After 13 months, Abobotulinum toxin A 1000 units were injected into detrusor. Ten days after the second Abobotulinum toxin A injection, she developed generalised muscle weakness. She had not regained full function in her arms and hands 8 months later.
Prior to bladder wall injection of Abobotulinum toxin A, this patient was not aware that she could develop muscle weakness albeit very rarely. Therefore, the patient made no association of the muscle weakness, which occurred after the first injection, to Abobotulinum toxin A. For this reason, she did not inform the clinicians that she developed weakness of upper limbs following Abobotulinum toxin A injection. As she was not informed of this side effect before the second bladder wall injection of Abobotulinum toxin A, she consented to undergo the repeat procedure and developed generalised muscle weakness.

Discussion
Patients should inform doctors the adverse effects of medical therapy so that future treatment is amended to ensure patient safety. Professional duty of candour states that doctors should discuss risks which occur often, those that are serious even if very unlikely, and those that are important to the patient.
Tamoxifen therapy in a murine model of myotubular myopathy
Authors: Maani Nika , Sabha Nesrin , Rezai Kamran , Ramani Arun , Groom Linda , Eltayeb Nadine , Mavandadnejad Faranak , Pang Andrea , Russo Giulia , Brudno Michael , Haucke Volker , Dirksen Robert T. , Dowling James J. 
Published: November 2018

AbstractMyotubular myopathy (MTM) is a severe X-linked disease without existing therapies. Here, we show that tamoxifen ameliorates MTM-related histopathological and functional abnormalities in mice, and nearly doubles survival. The beneficial effects of tamoxifen are mediated primarily via estrogen receptor signaling, as demonstrated through in vitro studies and in vivo phenotypic rescue with estradiol. RNA sequencing and protein expression analyses revealed that rescue is mediated in part through post-transcriptional reduction of dynamin-2, a known MTM modifier. These findings demonstrate an unexpected ability of tamoxifen to improve the murine MTM phenotype, providing preclinical evidence to support clinical translation.
A chromosome-scale assembly of the sorghum genome using nanopore sequencing and optical mapping
Authors: Deschamps Stéphane , Zhang Yun , Llaca Victor , Ye Liang , Sanyal Abhijit , King Matthew , May Gregory , Lin Haining 
Published: November 2018

AbstractLong-read sequencing technologies have greatly facilitated assemblies of large eukaryotic genomes. In this paper, Oxford Nanopore sequences generated on a MinION sequencer are combined with Bionano Genomics Direct Label and Stain (DLS) optical maps to generate a chromosome-scale de novo assembly of the repeat-rich Sorghum bicolor Tx430 genome. The final assembly consists of 29 scaffolds, encompassing in most cases entire chromosome arms. It has a scaffold N50 of 33.28 Mbps and covers 90% of the expected genome length. A sequence accuracy of 99.85% is obtained after aligning the assembly against Illumina Tx430 data and 99.6% of the 34,211 public gene models align to the assembly. Comparisons of Tx430 and BTx623 DLS maps against the public BTx623 v3.0.1 genome assembly suggest substantial discrepancies whose origin remains to be determined. In summary, this study demonstrates that informative assemblies of complex plant genomes can be generated by combining nanopore sequencing with DLS optical maps.
Crosstalks between mTORC1 and mTORC2 variagate cytokine signaling to control NK maturation and effector function
Authors: Wang Fangjie , Meng Meng , Mo Banghui , Yang Yao , Ji Yan , Huang Pei , Lai Wenjing , Pan Xiaodong , You Tingting , Luo Hongqin , Guan Xiao , Deng Yafei , Yuan Shunzong , Chu Jianhong , Namaka Michael , Hughes Tiffany , Ye Lilin , Yu Jianhua , Li Xiaohui , Deng Youcai 
Published: November 2018

AbstractThe metabolic checkpoint kinase mechanistic/mammalian target of rapamycin (mTOR) regulates natural killer (NK) cell development and function, but the exact underlying mechanisms remain unclear. Here, we show, via conditional deletion of Raptor (mTORC1) or Rictor (mTORC2), that mTORC1 and mTORC2 promote NK cell maturation in a cooperative and non-redundant manner, mainly by controlling the expression of Tbx21 and Eomes. Intriguingly, mTORC1 and mTORC2 regulate cytolytic function in an opposing way, exhibiting promoting and inhibitory effects on the anti-tumor ability and metabolism, respectively. mTORC1 sustains mTORC2 activity by maintaining CD122-mediated IL-15 signaling, whereas mTORC2 represses mTORC1-modulated NK cell effector functions by restraining STAT5-mediated SLC7A5 expression. These positive and negative crosstalks between mTORC1 and mTORC2 signaling thus variegate the magnitudes and kinetics of NK cell activation, and help define a paradigm for the modulation of NK maturation and effector functions.
Effective removal of mercury from aqueous streams via electrochemical alloy formation on platinum
Authors: Tunsu Cristian , Wickman Björn 
Published: November 2018

AbstractRetrieval of mercury from aqueous streams has significant environmental and societal importance due to its very high toxicity and mobility. We present here a method to retrieve mercury from aqueous feeds via electrochemical alloy formation on thin platinum films. This application is a green and effective alternative to traditional chemical decontamination techniques. Under applied potential, mercury ions in solution form a stable PtHg4alloy with platinum on the cathode. A 100 nanometres platinum film was fully converted to a 750 nanometres thick layer of PtHg4. The overall removal capacity is very high, > 88 g mercury per cm3. The electrodes can easily be regenerated after use. Efficient and selective decontamination is possible in a wide pH range, allowing processing of industrial, municipal, and natural waters. The method is suited for both high and low concentrations of mercury and can reduce mercury levels far below the limits allowed in drinking water.
Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement
Authors: Jia Guangshuai , Preussner Jens , Chen Xi , Guenther Stefan , Yuan Xuejun , Yekelchyk Michail , Kuenne Carsten , Looso Mario , Zhou Yonggang , Teichmann Sarah , Braun Thomas 
Published: November 2018

AbstractFormation and segregation of cell lineages forming the heart have been studied extensively but the underlying gene regulatory networks and epigenetic changes driving cell fate transitions during early cardiogenesis are still only partially understood. Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq). By leveraging on cell-to-cell transcriptome and chromatin accessibility heterogeneity, we identify different previously unknown cardiac subpopulations. Reconstruction of developmental trajectories reveal that multipotent Isl1+ CPC pass through an attractor state before separating into different developmental branches, whereas extended expression of Nkx2-5 commits CPC to an unidirectional cardiomyocyte fate. Furthermore, we show that CPC fate transitions are associated with distinct open chromatin states critically depending on Isl1 and Nkx2-5. Our data provide a model of transcriptional and epigenetic regulations during cardiac progenitor cell fate decisions at single-cell resolution.
Translation of non-standard codon nucleotides reveals minimal requirements for codon-anticodon interactions
Authors: Hoernes Thomas Philipp , Faserl Klaus , Juen Michael Andreas , Kremser Johannes , Gasser Catherina , Fuchs Elisabeth , Shi Xinying , Siewert Aaron , Lindner Herbert , Kreutz Christoph , Micura Ronald , Joseph Simpson , Höbartner Claudia , Westhof Eric , Hüttenhofer Alexander , Erlacher Matthias David 
Published: November 2018

AbstractThe precise interplay between the mRNA codon and the tRNA anticodon is crucial for ensuring efficient and accurate translation by the ribosome. The insertion of RNA nucleobase derivatives in the mRNA allowed us to modulate the stability of the codon-anticodon interaction in the decoding site of bacterial and eukaryotic ribosomes, allowing an in-depth analysis of codon recognition. We found the hydrogen bond between the N1 of purines and the N3 of pyrimidines to be sufficient for decoding of the first two codon nucleotides, whereas adequate stacking between the RNA bases is critical at the wobble position. Inosine, found in eukaryotic mRNAs, is an important example of destabilization of the codon-anticodon interaction. Whereas single inosines are efficiently translated, multiple inosines, e.g., in the serotonin receptor 5-HT2C mRNA, inhibit translation. Thus, our results indicate that despite the robustness of the decoding process, its tolerance toward the weakening of codon-anticodon interactions is limited.
A continuous-time MaxSAT solver with high analog performance
Authors: Molnár Botond , Molnár Ferenc , Varga Melinda , Toroczkai Zoltán , Ercsey-Ravasz Mária 
Published: November 2018

AbstractMany real-life optimization problems can be formulated in Boolean logic as MaxSAT, a class of problems where the task is finding Boolean assignments to variables satisfying the maximum number of logical constraints. Since MaxSAT is NP-hard, no algorithm is known to efficiently solve these problems. Here we present a continuous-time analog solver for MaxSAT and show that the scaling of the escape rate, an invariant of the solver’s dynamics, can predict the maximum number of satisfiable constraints, often well before finding the optimal assignment. Simulating the solver, we illustrate its performance on MaxSAT competition problems, then apply it to two-color Ramsey number R(m, m) problems. Although it finds colorings without monochromatic 5-cliques of complete graphs on N ≤ 42 vertices, the best coloring for N = 43 has two monochromatic 5-cliques, supporting the conjecture that R(5, 5) = 43. This approach shows the potential of continuous-time analog dynamical systems as algorithms for discrete optimization.
Hidden diversity of soil giant viruses
Authors: Schulz Frederik , Alteio Lauren , Goudeau Danielle , Ryan Elizabeth M. , Yu Feiqiao B. , Malmstrom Rex R. , Blanchard Jeffrey , Woyke Tanja 
Published: November 2018

AbstractKnown giant virus diversity is currently skewed towards viruses isolated from aquatic environments and cultivated in the laboratory. Here, we employ cultivation-independent metagenomics and mini-metagenomics on soils from the Harvard Forest, leading to the discovery of 16 novel giant viruses, chiefly recovered by mini-metagenomics. The candidate viruses greatly expand phylogenetic diversity of known giant viruses and either represented novel lineages or are affiliated with klosneuviruses, Cafeteria roenbergensis virus or tupanviruses. One assembled genome with a size of 2.4 Mb represents the largest currently known viral genome in the Mimiviridae, and others encode up to 80% orphan genes. In addition, we find more than 240 major capsid proteins encoded on unbinned metagenome fragments, further indicating that giant viruses are underexplored in soil ecosystems. The fact that most of these novel viruses evaded detection in bulk metagenomes suggests that mini-metagenomics could be a valuable approach to unearth viral giants.
Memory formation and long-term maintenance of IL-7Rα+ ILC1s via a lymph node-liver axis
Authors: Wang Xianwei , Peng Hui , Cong Jingjing , Wang Xuefu , Lian Zhexiong , Wei Haiming , Sun Rui , Tian Zhigang 
Published: November 2018

AbstractNatural killer (NK) cells are reported to have immunological memory, with CD49a+ liver-resident NK cells shown to confer hapten-specific memory responses, but how this memory is induced or maintained is unclear. Here we show that memory type I innate lymphoid cells (ILC1s), which express IL-7Rα, are generated in the lymph nodes (LNs) and require IL-7R signaling to maintain their longevity in the liver. Hapten sensitization initiates CXCR3-dependent recruitment of IL-7Rα+ ILC1s into skin-draining LNs, where they are primed and acquire hapten-specific memory potential. Memory IL-7Rα+ ILC1s then exit draining LNs and are preferentially recruited, via CXCR6, to reside in the liver. Moreover, long-term blockade of IL-7R signaling significantly reduces ILC1-mediated memory responses. Thus, our results identify a memory IL-7Rα+ ILC1 population and reveal a LN-liver axis that is essential for ILC1 memory generation and long-term maintenance.
Decreased BDNF Release in Cortical Neurons of a Knock-in Mouse Model of Huntington’s Disease
Authors: Yu Chenglong , Li Chun Hei , Chen Sidong , Yoo Hanna , Qin Xianan , Park Hyokeun 
Published: November 2018

AbstractHuntington’s disease (HD) is a dominantly inherited neurodegenerative disease caused by an increase in CAG repeats in the Huntingtin gene (HTT). The striatum is one of the most vulnerable brain regions in HD, and altered delivery of BDNF to the striatum is believed to underlie this high vulnerability. However, the delivery of BDNF to the striatum in HD remains poorly understood. Here, we used real-time imaging to visualize release of BDNF from cortical neurons cultured alone or co-cultured with striatal neurons. BDNF release was significantly decreased in the cortical neurons of zQ175 mice (a knock-in model of HD), and total internal reflection fluorescence microscopy revealed several release patterns of single BDNF-containing vesicles, with distinct kinetics and prevalence, in co-cultured cortical HD neurons. Notably, a smaller proportion of single BDNF-containing vesicles underwent full release in HD neurons than in wild-type neurons. This decreased release of BDNF in cortical neurons might lead to decreased BDNF levels in the striatum because the striatum receives BDNF mainly from the cortex. In addition, we observed a decrease in the total travel length and speed of BDNF-containing vesicles in HD neurons, indicating altered transport of these vesicles in HD. Our findings suggest a potential mechanism for the vulnerability of striatal neurons in HD and offer new insights into the pathogenic mechanisms underlying the degeneration of neurons in HD.
Access to high-impact mutations constrains the evolution of antibiotic resistance in soft agar
Authors: Ghaddar Nour , Hashemidahaj Mona , Findlay Brandon L. 
Published: November 2018

AbstractDespite widespread resistance to many important antibiotics, the factors that govern the emergence and prevalence of antibiotic-resistant bacteria are still unclear. When exposed to antibiotic gradients in soft agar plates measuring as little as 1.25 × 11 cm we found that Escherichia coli rapidly became resistant to representatives from every class of antibiotics active against Gram-negative bacteria. Evolution kinetics were independent of the frequency of spontaneous mutations that confer antibiotic resistance or antibiotic dose-response curves, and were only loosely correlated to maximal antibiotic concentrations. Instead, rapid evolution required unrealized mutations that could markedly decrease antibiotic susceptibility. When bacteria could not evolve through these “high-impact” mutations, populations frequently bottlenecked, reducing the number of cells from which mutants could arise and prolonging evolution times. This effect was independent of the antibiotic’s mechanism of action, and may affect the evolution of antibiotic resistance in clinical settings.
Comparative genome-wide analysis of WRKY transcription factors in two Asian legume crops: Adzuki bean and Mung bean
Authors: Srivastava Richa , Kumar Sanjeev , Kobayashi Yasufumi , Kusunoki Kazutaka , Tripathi Prateek , Kobayashi Yuriko , Koyama Hiroyuki , Sahoo Lingaraj 
Published: November 2018

AbstractThe seminal participation of WRKY transcription factors in plant development, metabolism and in the governance of defense mechanism implicated their gaining importance for genomic and functional studies. The recent release of draft genome sequences of two legume crops, Adzuki bean (Vigna angularis) and Mung bean (Vigna radiata) has paved the way for characterization of WRKY gene family in these crops. We found 84WRKYgenes in Adzuki bean (VaWRKY) and 85WRKYgenes in Mung bean (VrWRKY). Based on the phylogenetic analysis,VaWRKYgenes were classified into three groups with 15 members in Group I, 56 members in Group II, and 13 members in Group III, which was comparable toVrWRKYdistribution in Mung bean, 16, 56 and 13 members in Group I, II and III, respectively. The few tandem and segmental duplication events suggested that recent duplication plays no prominent role in the expansionVaWRKYandVrWRKYgenes. The illustration of gene-structure and their encoded protein-domains further revealed the nature of WRKY proteins. Moreover, the identification of abiotic or biotic stress-responsivecis-regulatory elements in the promoter regions of someWRKYgenes provides fundamental insights for their further implementation in stress-tolerance and genetic improvement of agronomic traits.
Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents
Authors: Hagerman Randi , Jacquemont Sebastien , Berry-Kravis Elizabeth , Des Portes Vincent , Stanfield Andrew , Koumaras Barbara , Rosenkranz Gerd , Murgia Alessandra , Wolf Christian , Apostol George , von Raison Florian 
Published: November 2018

AbstractFragile X syndrome (FXS) is the most common monogenic cause of inherited intellectual and developmental disabilities. Mavoglurant, a selective metabotropic glutamate receptor subtype-5 antagonist, has shown positive neuronal and behavioral effects in preclinical studies, but failed to demonstrate any behavioral benefits in two 12-week, randomized, placebo-controlled, double-blind, phase IIb studies in adults and adolescents with FXS. Here we report the long-term safety (primary endpoint) and efficacy (secondary endpoint) results of the open-label extensions. Adolescent (n = 119, aged 12–19 years) and adult (n = 148, aged 18–45 years) participants received up to 100 mg bid mavoglurant for up to 34 months. Both extension studies were terminated prematurely due to lack of proven efficacy in the core studies. Mavoglurant was well tolerated with no new safety signal. Five percent of adults and 16.9 percent of adolescents discontinued treatment due to adverse events. Gradual and consistent behavioral improvements as measured by the ABC-CFX scale were observed, which were numerically superior to those seen in the placebo arm of the core studies. These two extension studies confirm the long-term safety of mavoglurant in FXS, but further investigations are required to determine whether and under which conditions the significant preclinical results obtained with mGluR5 inhibition can translate to humans.
A Novel Targeted Analysis of Peripheral Steroids by Ultra-Performance Supercritical Fluid Chromatography Hyphenated to Tandem Mass Spectrometry
Authors: de Kock Neil , Acharya Santosh R. , Ubhayasekera S. J. Kumari A. , Bergquist Jonas 
Published: November 2018

AbstractUltra-performance supercritical fluid chromatography–tandem mass spectrometry (UPSFC–MS/MS) is an alternative method for steroid analysis. Continuous development of analytical methodologies for steroid profiling is of major importance in the clinical environment to provide useful and more comprehensive data. The aim of this study was to identify and quantify a large number of endogenous steroids from the four major classes (estrogens, androgens, progestogens and corticosteroids) simultaneously within a short analytical time. This novel UPSFC–MS/MS method with electrospray in positive ionisation (ESI+) mode is robust, selective and present sufficiently high sensitivity to profile nineteen steroids in 50 µL human plasma. Under optimised conditions, nineteen different steroids were separated with high efficiency in the multiple reaction monitoring (MRM) mode. The linearity of the method was good with correlation coefficients (R2) in the range of 0.9983–0.9999 and with calibration range from 0.05–500 ng/mL in human plasma. The intraday and interday precision of the method, as RSD, was less than 15%. The accuracy of the nineteen analytes varied between 80 to 116%. Finally, the novel method was successfully applied for the determination of nineteen steroids within 5 minutes providing the possibility to use it for research as well as routine healthcare practice.