bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovering the atmospheres of hot Jupiters
Authors: Cauley P. Wilson 
Published: September 2020

AbstractHot Jupiters are an extraordinary class of exoplanets, orbiting their host stars with periods of hours to a few days. Some of these objects have day-side temperatures approaching photospheric temperatures of late K-type stars. I will give an overview of how we characterize the atmospheres of these fascinating objects and some the more recent exciting results to come from ground and space-based telescopes, as well as what the future holds for detailed characterization of short-period exoplanet atmospheres.
Probing solar-cycle variations of magnetic fields in the convection zone using meridional flows
Authors: Lin Chia-Hsien , Chou Dean-Yi 
Published: September 2020

AbstractSolar magnetic fields are believed to originate from the base of convection zone. However, it has been difficult to obtain convincing observational evidence of the magnetic fields in the deep convection zone. The goal of this study is to investigate whether solar meridional flows can be used to detect the magnetic-field effects. Meridional flows are axisymmetric flows on the meridional plane. Our result shows that the flow pattern in the entire convection zone changes significantly from solar minimum to maximum. The changes all centered around active latitudes, suggesting that the magnetic fields are responsible for the changes. The results indicate that the meridional flow can be used to detect the effects of magnetic field in the deep convection zone.The results have been published in the Astrophysical Journal (lc2018).
3D Modeling of the Structure and Dynamics of a Main-Sequence F-type Star
Authors: Kitiashvili Irina N. , Wray Alan A. 
Published: September 2020

AbstractCurrent state-of-the-art computational modeling makes it possible to build realistic models of stellar convection zones and atmospheres that take into account chemical composition, radiative effects, ionization, and turbulence. The standard 1D mixing-length-based evolutionary models are not able to capture many physical processes of the stellar interior dynamics. Mixing-length models provide an initial approximation of stellar structure that can be used to initialize 3D radiative hydrodynamics simulations which include realistic modeling of turbulence, radiation, and other phenomena.In this paper, we present 3D radiative hydrodynamic simulations of an F-type main-sequence star with 1.47 solar mass. The computational domain includes the upper layers of the radiation zone, the entire convection zone, and the photosphere. The effects of stellar rotation is modeled in the f-plane approximation. These simulations provide new insight into the properties of the convective overshoot region, the dynamics of the near-surface, highly turbulent layer, and the structure and dynamics of granulation. They reveal solar-type differential rotation and latitudinal dependence of the tachocline location.
Observational constraints for solar-type Stellar winds
Authors: Güdel Manuel 
Published: September 2020

AbstractIonized winds from late-type main-sequence stars are important for stellar spin-down and therefore the evolution of stellar activity; winds blow an “astrosphere” into the interstellar medium that absorbs a large part of galactic cosmic rays; and the winds play a key role in shaping planetary environments, in particular their upper atmospheres. These issues have been well studied for the solar wind but little is known about winds escaping from other solar-type stars. Several methods have been devised to either detect winds directly or to infer the presence of such winds from features that are shaped by the winds. This paper summarizes these methods and discusses exemplary findings. There is need for more studies using multiple methods for the same stars.
Assimilation of the Rain Gauge Measurements Using Particle Filter
Authors: Kumar Prashant 
Published: September 2020

AbstractThe well‐recognized constraint of nonlinear and non‐Gaussian distribution of rainfall observation limits its assimilation in the high‐dimensional numerical weather prediction (NWP) model. In this study, rainfall observed from Indian Meteorological Department (IMD) rain gauges over Indian landmass is assimilated in the Weather Research and Forecasting (WRF) model using particle filter. In the framework of imperfect weather models, particles (or ensembles) for rainfall predictions are created with various combinations of model physics (viz., cumulus parameterization, microphysics and planetary boundary layer schemes). The multiple hypotheses are used to determine the weights for different particles, and this is the step where IMD rainfall data are used for assimilation. Further, a resampling step is performed to generate new particles from high weight particles using stochastic kinetic‐energy backscatter scheme (SKEBS) method in which dynamical variables are perturbed into the model physics. Results, based on rainfall verification scores, suggest that the assimilation of the rainfall using particle filter could improve the prediction of rainfall over CNT runs (unweighted particles; without assimilation). Moreover, surface and vertical profile of temperature, water vapor mixing ratio (WVMR), and wind speed are also improved in 24‐hr forecasts.
CRISPR/Cas9 genome-wide loss-of-function screening identifies druggable cellular factors involved in sunitinib resistance in renal cell carcinoma
Authors: Makhov Peter , Sohn Ji A. , Serebriiskii Ilya G. , Fazliyeva Rushaniya , Khazak Vladimir , Boumber Yanis , Uzzo Robert G. , Kolenko Vladimir M. 
Published: September 2020

Abstract
Background
Multi-targeted tyrosine kinase inhibitors (TKIs) are the standard of care for patients with advanced clear cell renal cell carcinoma (ccRCC). However, a significant number of ccRCC patients are primarily refractory to targeted therapeutics, showing neither disease stabilisation nor clinical benefits.

Methods
We used CRISPR/Cas9-based high-throughput loss of function (LOF) screening to identify cellular factors involved in the resistance to sunitinib. Next, we validated druggable molecular factors that are synthetically lethal with sunitinib treatment using cell and animal models of ccRCC.

Results
Our screening identified farnesyltransferase among the top hits contributing to sunitinib resistance in ccRCC. Combined treatment with farnesyltransferase inhibitor lonafarnib potently augmented the anti-tumour efficacy of sunitinib both in vitro and in vivo.

Conclusion
CRISPR/Cas9 LOF screening presents a promising approach to identify and target cellular factors involved in the resistance to anti-cancer therapeutics.
NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy
Authors: McTiernan Nina , Gill Harinder , Prada Carlos E. , Pachajoa Harry , Lores Juliana ,   CAUSES study, Arnesen Thomas 
Published: September 2020

AbstractNearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.
Mean amplitude of intraocular pressure excursions: a new assessment parameter for 24-h pressure fluctuations in glaucoma patients
Authors: Zhai Ruyi , Cheng Jingyi , Xu Huan , Fang Zhaobin , Chen Xu , Qiu Siyu , Sun Xinghuai , Lee Richard K. , Xiao Ming , Kong Xiangmei 
Published: September 2020

Abstract
Background
Intraocular pressure (IOP) is important in the pathogenesis of glaucoma and its circadian fluctuations are important in the disease management; however, there are no adequate parameters to describe the fluctuations. This study investigates a new parameter, mean amplitude of intraocular pressure excursion (MAPE), and compares its ability in assessing 24-h IOP fluctuations with other ocular parameters.

Methods
Only the right eye was evaluated in each of the 79 healthy people and 164 untreated patients with primary open angle glaucoma (POAG). Each participant underwent 24-h IOP monitoring by measuring IOP every 2 h. IOP fluctuations were expressed as MAPE calculations and currently used parameters included mean IOP, standard deviation of IOP, max difference and area under the circadian IOP curve. Comprehensive ophthalmologic examinations were also performed. Associations between visual field deficits and IOP fluctuation parameters were investigated via partial least squares (PLS) regression. Diagnostic performance was evaluated with area under the receiver operating characteristic curves (ROC).

Results
Compared with healthy volunteers, the MAPE values in POAG patients were higher (4.16 ± 1.90 versus 2.45 ± 0.89, p < 0.01). In PLS regressions where visual field deficits were as dependent variable, MAPE had the highest score regarding variable importance in projection, and its standard regression coefficient was larger than other parameters. Diagnostic performance analysis showed the area under ROC of MAPE for glaucoma detection was 0.822 (0.768–0.868, p < 0.001).

Conclusions
MAPE might be an effective parameter in clinic to characterise IOP circadian fluctuations.
The stability of envelope-pseudotyped lentiviral vectors
Authors: Dautzenberg Iris J. C. , Rabelink Martijn J. W. E. , Hoeben Rob C. 
Published: September 2020

AbstractLentiviral vectors have become popular tools for stable genetic modification of mammalian cells. In some applications of lentiviral vector-transduced cells, infectious-lentiviral particles should be absent. Quantification of the free-vector particles that remain from the inoculum can be difficult. Therefore a formula was established that yields an estimation of the ‘Reduction Ratio.’ This ratio represents the loss of titer based on a number of vector-inactivating effects. In this study, we evaluated several parameters and assumptions that were used in the current formula. We generated new data on the stability and trypsin sensitivity of lentiviral vectors pseudotyped with eight heterologous envelope proteins and the loss of vectors by washing or passaging the cell cultures. Our data demonstrate that the loss of virus titer under the influence of trypsin as well as the half-life of the particles in tissue culture medium is dependent on the vector’s envelope protein. While VSV-G-envelope-pseudotyped particles were unsensitive to trypsin, the titer of vectors pseudotyped with other envelope proteins decreased 2–110-fold. The half-life in culture medium ranged from 8 to 40 h for the different envelope-pseudotyped vectors, with 35 h for VSV-G-envelope-pseudotyped vector particles. Additionally, we found that removal of the culture medium from Ø35 mm to Ø10 cm dishes reduces the amount of vector particles in the culture by 50-fold and 20-fold, respectively. Together these data can be used to more precisely estimate the maximum number of free lentiviral vector particles in cell cultures.
Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis
Authors: Bogdanow Boris , Schmidt Max , Weisbach Henry , Gruska Iris , Vetter Barbara , Imami Koshi , Ostermann Eleonore , Brune Wolfram , Selbach Matthias , Hagemeier Christian , Wiebusch Lüder 
Published: September 2020

AbstractHerpesviruses encode conserved protein kinases (CHPKs) to stimulate phosphorylation-sensitive processes during infection. How CHPKs bind to cellular factors and how this impacts their regulatory functions is poorly understood. Here, we use quantitative proteomics to determine cellular interaction partners of human herpesvirus (HHV) CHPKs. We find that CHPKs can target key regulators of transcription and replication. The interaction with Cyclin A and associated factors is identified as a signature of β-herpesvirus kinases. Cyclin A is recruited via RXL motifs that overlap with nuclear localization signals (NLS) in the non-catalytic N termini. This architecture is conserved in HHV6, HHV7 and rodent cytomegaloviruses. Cyclin A binding competes with NLS function, enabling dynamic changes in CHPK localization and substrate phosphorylation. The cytomegalovirus kinase M97 sequesters Cyclin A in the cytosol, which is essential for viral inhibition of cellular replication. Our data highlight a fine-tuned and physiologically important interplay between a cellular cyclin and viral kinases.
A possible universal role for mRNA secondary structure in bacterial translation revealed using a synthetic operon
Authors: Chemla Yonatan , Peeri Michael , Heltberg Mathias Luidor , Eichler Jerry , Jensen Mogens Høgh , Tuller Tamir , Alfonta Lital 
Published: September 2020

AbstractIn bacteria, translation re-initiation is crucial for synthesizing proteins encoded by genes that are organized into operons. The mechanisms regulating translation re-initiation remain, however, poorly understood. We now describe the ribosome termination structure (RTS), a conserved and stable mRNA secondary structure localized immediately downstream of stop codons, and provide experimental evidence for its role in governing re-initiation efficiency in a synthetic Escherichia coli operon. We further report that RTSs are abundant, being associated with 18%–65% of genes in 128 analyzed bacterial genomes representing all phyla, and are selectively depleted when translation re-initiation is advantageous yet selectively enriched so as to insulate translation when re-initiation is deleterious. Our results support a potentially universal role for the RTS in controlling translation termination-insulation and re-initiation across bacteria.
ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration
Authors: Kidiyoor Gururaj Rao , Li Qingsen , Bastianello Giulia , Bruhn Christopher , Giovannetti Irene , Mohamood Adhil , Beznoussenko Galina V. , Mironov Alexandre , Raab Matthew , Piel Matthieu , Restuccia Umberto , Matafora Vittoria , Bachi Angela , Barozzi Sara , Parazzoli Dario , Frittoli Emanuela , Palamidessi Andrea , Panciera Tito , Piccolo Stefano , Scita Giorgio , Maiuri Paolo , Havas Kristina M. , Zhou Zhong-Wei , Kumar Amit , Bartek Jiri , Wang Zhao-Qi , Foiani Marco 
Published: September 2020

AbstractATR responds to mechanical stress at the nuclear envelope and mediates envelope-associated repair of aberrant topological DNA states. By combining microscopy, electron microscopic analysis, biophysical and in vivo models, we report that ATR-defective cells exhibit altered nuclear plasticity and YAP delocalization. When subjected to mechanical stress or undergoing interstitial migration, ATR-defective nuclei collapse accumulating nuclear envelope ruptures and perinuclear cGAS, which indicate loss of nuclear envelope integrity, and aberrant perinuclear chromatin status. ATR-defective cells also are defective in neuronal migration during development and in metastatic dissemination from circulating tumor cells. Our findings indicate that ATR ensures mechanical coupling of the cytoskeleton to the nuclear envelope and accompanying regulation of envelope-chromosome association. Thus the repertoire of ATR-regulated biological processes extends well beyond its canonical role in triggering biochemical implementation of the DNA damage response.
Correlation between the static and dynamic responses of organic single-crystal field-effect transistors
Authors: Sawada Taiki , Yamamura Akifumi , Sasaki Mari , Takahira Kayo , Okamoto Toshihiro , Watanabe Shun , Takeya Jun 
Published: September 2020

AbstractTransistors, the most important logic elements, are maintained under dynamic influence during circuit operations. Practically, circuit design protocols and frequency responsibility should stem from a perfect agreement between the static and dynamic properties. However, despite remarkable improvements in mobility for organic semiconductors, the correlation between the device performances achieved under static and dynamic circumstances is controversial. Particularly in the case of organic semiconductors, it remains unclear whether parasitic elements that relate to their unique molecular aggregates may violate the radiofrequency circuit model. Thus, we herein report the manufacture of micrometre-scale transistor arrays composed of solution-processed organic semiconductors, which achieve near very high-frequency band operations. Systematic investigations into the device geometrical factors revealed that the radiofrequency circuit model established on a solid-state continuous medium is extendable to organic single-crystal field-effect transistors. The validity of this radiofrequency circuit model allows a reliable prediction of the performances of organic radiofrequency devices.
Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila
Authors: Trastoy Beatriz , Naegeli Andreas , Anso Itxaso , Sjögren Jonathan , Guerin Marcelo E. 
Published: September 2020

AbstractAkkermansia muciniphilais a mucin-degrading bacterium commonly found in the human gut that promotes a beneficial effect on health, likely based on the regulation of mucus thickness and gut barrier integrity, but also on the modulation of the immune system. In this work, we focus in OgpA fromA. muciniphila, anO-glycopeptidase that exclusively hydrolyzes the peptide bondN-terminal to serine or threonine residues substituted with anO-glycan. We determine the high-resolution X-ray crystal structures of the unliganded form of OgpA, the complex with the glycodrosocinO-glycopeptide substrate and its product, providing a comprehensive set of snapshots of the enzyme along the catalytic cycle. In combination withO-glycopeptide chemistry, enzyme kinetics, and computational methods we unveil the molecular mechanism ofO-glycan recognition and specificity for OgpA. The data also contribute to understanding howA. muciniphilaprocesses mucins in the gut, as well as analysis of post-translationalO-glycosylation events in proteins.
Dependence of DNA length on binding affinity between TrpR and trpO of DNA
Authors: Shimamoto Nobuo , Toda Mikito , Nara Shigetoshi , Komatsuzaki Tamiki , Kamagata Kiyoto , Kinebuchi Takashi , Tomizawa Jun-ichi 
Published: September 2020

AbstractWe scrutinize the length dependency of the binding affinity of bacterial repressor TrpR protein to trpO (specific site) on DNA. A footprinting experiment shows that the longer the DNA length, the larger the affinity of TrpR to the specific site on DNA. This effect termed “antenna effect” might be interpreted as follows: longer DNA provides higher probability for TrpR to access to the specific site aided by one-dimensional diffusion along the nonspecific sites of DNA. We show that, however, the antenna effect cannot be explained while detailed balance holds among three kinetic states, that is, free protein/DNA, nonspecific complexes, and specific complex. We propose a working hypothesis that slow degree(s) of freedom in the system switch(es) different potentials of mean force causing transitions among the three states. This results in a deviation from detailed balance on the switching timescale. We then derive a simple reaction diffusion/binding model that describes the antenna effect on TrpR binding to its target operator. Possible scenarios for such slow degree(s) of freedom in TrpR–DNA complex are addressed.
Blood biomarkers indicate that the preclinical stages of Alzheimer's disease present overlapping molecular features
Authors: Di Costanzo Alfonso , Paris Debora , Melck Dominique , Angiolillo Antonella , Corso Gaetano , Maniscalco Mauro , Motta Andrea 
Published: September 2020

AbstractIt is still debated whether non-specific preclinical symptoms of Alzheimer’s disease (AD) can have diagnostic relevance. We followed the evolution from cognitively normal to AD by NMR-based metabolomics of blood sera. Multivariate statistical analysis of the NMR profiles yielded models that discriminated subjective memory decline (SMD), mild cognitive impairment (MCI) and AD. We validated a panel of six statistically significant metabolites that predicted SMD, MCI and AD in a blind cohort with sensitivity values ranging from 88 to 95% and receiver operating characteristic values from 0.88 to 0.99. However, lower values of specificity, accuracy and precision were observed for the models involving SMD and MCI, which is in line with the pathological heterogeneity indicated by clinical data. This excludes a “linear” molecular evolution of the pathology, pointing to the presence of overlapping “gray-zones” due to the reciprocal interference of the intermediate stages. Yet, the clear difference observed in the metabolic pathways of each model suggests that pathway dysregulations could be investigated for diagnostic purposes.
Generation of myostatin edited horse embryos using CRISPR/Cas9 technology and somatic cell nuclear transfer
Authors: Moro Lucia Natalia , Viale Diego Luis , Bastón Juan Ignacio , Arnold Victoria , Suvá Mariana , Wiedenmann Elisabet , Olguín Martín , Miriuka Santiago , Vichera Gabriel 
Published: September 2020

AbstractThe application of new technologies for gene editing in horses may allow the generation of improved sportive individuals.
Here, we aimed to knock out the myostatin gene (MSTN), a negative regulator of muscle mass development, using CRISPR/Cas9 and to generate edited embryos for the first time in horses. We nucleofected horse fetal fibroblasts with 1, 2 or 5 µg of 2 different gRNA/Cas9 plasmids targeting the first exon of MSTN. We observed that increasing plasmid concentrations improved mutation efficiency. The average efficiency was 63.6% for gRNA1 (14/22 edited clonal cell lines) and 96.2% for gRNA2 (25/26 edited clonal cell lines). Three clonal cell lines were chosen for embryo generation by somatic cell nuclear transfer: one with a monoallelic edition, one with biallelic heterozygous editions and one with a biallelic homozygous edition, which rendered edited blastocysts in each case. Both MSTN editions and off-targets were analyzed in the embryos. In conclusion, CRISPR/Cas9 proved an efficient method to edit the horse genome in a dose dependent manner with high specificity. Adapting this technology sport advantageous alleles could be generated, and a precision breeding program could be developed.