bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGF signal is not required for hepatoblast differentiation of human iPS cells
Authors: Toba Yukiko , Kiso Ayumi , Nakamae Souichiro , Sakurai Fuminori , Takayama Kazuo , Mizuguchi Hiroyuki 
Published: March 2019

AbstractHuman induced pluripotent stem cell-derived hepatocyte-like cells are expected to be utilized in pharmaceutical research and regenerative medicine. In general, human induced pluripotent stem (iPS) cells are differentiated into hepatocyte-like cells through definitive endoderm cells and hepatoblast-like cells using various growth factors that are essential for liver development. Although recombinant bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) are widely used in the hepatoblast differentiation, hepatoblast differentiation process has not been fully modified. In this study, we examined the roles of BMPs and FGFs in the hepatoblast differentiation from human iPS cells. Surprisingly, the gene expression levels of hepatoblast markers were upregulated by the removal of FGFs. In addition, the percentages of hepatoblast markers-positive cells were increased by the removal of FGFs. Furthermore, the hepatocyte differentiation potency was also significantly increased by the removal of FGFs. To examine whether FGF signals are completely unnecessary for the hepatoblast differentiation, the expression levels of endogenous FGF ligands and receptors were examined. The definitive endoderm cells highly expressed the FGF ligand, FGF2, and the FGF receptor, FGFR1. To examine the role of endogenous FGF signals, an FGFR inhibitor was treated during the hepatoblast differentiation. The hepatoblast differentiation was promoted by using FGFR inhibitor, suggesting that endogenous FGF signals are also unnecessary for the hepatoblast differentiation. In conclusion, we found that FGF signals are not essential for hepatoblast differentiation. We believe that our finding will be useful for generating functional hepatocyte-like cells for medical applications.
Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes
Authors: Müller Dominik , Hagenah Dorian , Biswanath Santoshi , Coffee Michelle , Kampmann Andreas , Zweigerdt Robert , Heisterkamp Alexander , Kalies Stefan M. K. 
Published: March 2019

AbstractA highly organized cytoskeleton architecture is the basis for continuous and controlled contraction in cardiomyocytes (CMs). Abnormalities in cytoskeletal elements, like the Z-disc, are linked to several diseases. It is challenging to reveal the mechanisms of CM failure, endogenous repair, or mechanical homeostasis on the scale of single cytoskeletal elements. Here, we used a femtosecond (fs) laser to ablate single Z-discs in human pluripotent stem cells (hPSC) -derived CMs (hPSC-CM) and neonatal rat CMs. We show, that CM viability was unaffected by the loss of a single Z-disc. Furthermore, more than 40% of neonatal rat and 68% of hPSC-CMs recovered the Z-disc loss within 24 h. Significant differences to control cells, after the Z-disc loss, in terms of cell perimeter, x- and y-expansion and calcium homeostasis were not found. Only 14 days in vitro old hPSC-CMs reacted with a significant decrease in cell area, x- and y-expansion 24 h past nanosurgery. This demonstrates that CMs can compensate the loss of a single Z-disc and recover a regular sarcomeric pattern during spontaneous contraction. It also highlights the significant potential of fs laser-based nanosurgery to physically micro manipulate CMs to investigate cytoskeletal functions and organization of single elements.
Effect of size and charge asymmetry on aggregation kinetics of oppositely charged nanoparticles
Authors: Singh Kulveer , Raghav Anubhav , Jha Prateek K. , Satapathi Soumitra 
Published: March 2019

AbstractWe report a theoretical and experimental study of the aggregation kinetics of oppositely charged nanoparticles. Kinetic Monte Carlo simulations are performed for symmetric, charge-asymmetric and size-asymmetric systems of oppositely charged nanoparticles. Simulation results show that both the weight and number average aggregate size kinetics exhibit power law scaling with different exponents for small and intermediate time of evolution. The qualitative behavior of the symmetric and the size asymmetric system are the same, but the charge asymmetric system shows anomalous behavior for intermediate to high particle concentrations. We also observe a strong dependence of power law exponents on the particle concentration. Radius of gyration of the cluster that indicates how nanoparticles inside a cluster are distributed around the center of mass of the cluster shows a non-monotonic time evolution with pronounced peak at higher particle concentration. The dependence of particle concentration on aggregation kinetics as observed by predictive numerical simulation is further verified experimentally by monitoring the time evolution of aggregate size of nanoparticles assemblies of Poly (methacrylic acid) (PMMA) nanoparticles functionalized with oppositely charged ligands. These size and charge tunable asymmetric polymeric nanoparticles were synthesized by modified miniemulsion technique. The integrated approach for studying nanoparticles aggregation as described here renders new insights into super structure formation and morphology optimization which can be potentially useful in the design of new materials, such as organic photovoltaics.
Resting hyperinflation and emphysema on the clinical course of COPD
Authors: Kim Yeon Wook , Lee Chang-Hoon , Hwang Hun-Gyu , Kim Yu-Il , Kim Deog Kyeom , Oh Yeon-Mok , Lee Sang Haak , Kim Ki Uk , Lee Sang-Do 
Published: March 2019

AbstractThe aim of this study is to clarify whether the combined evaluation of resting hyperinflation and emphysema confers any additional advantages in terms of predicting clinical outcomes in chronic obstructive pulmonary disease (COPD) patients. We included COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. Patients with a residual volume/total lung capacity (RV/TLC) over the upper limit of normal were defined as having resting hyperinflation, and those with an emphysema index >10% were defined as having emphysema. We investigated the impacts of resting hyperinflation and emphysema on exacerbations and mortality. A total of 310 COPD patients were analyzed over a mean of 61.1 months. After adjustment for covariates, resting hyperinflation was an independent predictor of earlier exacerbation (HR = 1.66, CI = 1.24–2.22), more frequent exacerbation (IRR = 1.35, CI = 1.01–1.81), and higher mortality (HR = 2.45, CI = 1.16–5.17) risk. Emphysema was also significantly associated with earlier exacerbation (HR = 1.64, CI = 1.15–2.35), and higher mortality (HR = 3.13, CI = 1.06–9.27) risk. Participants with both resting hyperinflation and emphysema had an additively higher risk of earlier exacerbations (HR = 1.71, 95% CI = 1.26–2.33) and mortality (HR = 3.75, 95% CI = 1.81–7.73) compared with those in other groups. In conclusion, resting hyperinflation and emphysema had additional worse impacts on exacerbations and mortality in COPD patients.
Optimal leaf water status regulation of plants in drylands
Authors: Ratzmann Gregor , Zakharova Liubov , Tietjen Britta 
Published: March 2019

AbstractLeaf water potential regulation is a key process in whole plant and ecosystem functioning. While low water potentials induced by open stomata may initially be associated with greater CO2 supply and a higher water flux from the rhizosphere to the canopy, they also inhibit cell growth, photosynthesis and ultimately water supply. Here, we show that plants regulate their leaf water potential in an optimal manner under given constraints using a simple leaf water status regulation model and data from a global dryland leaf water potential database. Model predictions agree strongly with observations across locations and species and are further supported by experimental data. Leaf water potentials non-linearly decline with soil water potential, underlining the shift from maximizing water supply to avoiding stress with declining water availability. Our results suggest that optimal regulation of the leaf water status under varying water supply and stress tolerance is a ubiquitous property of plants in drylands. The proposed model moreover provides a novel quantitative framework describing how plants respond to short- and long-term changes in water availability and may help elaborating models of plant and ecosystem functioning.
Preparation of peroxidase and phenolics using discarded sweet potato old stems
Authors: Yang Liu , Xi Yi , Luo Xiang-Yu , Ni He , Li Hai-Hang 
Published: March 2019

AbstractSweet potato (Ipomoea batatas L.) is the sixth most important food crop in the world. The industry discarded huge amount of sweet potato stems, rich of peroxidases and phenolics. A simple procedure was developed to make peroxidases and phenolics from sweet potato old stems. Dried stem powder was loaded into columns with water and eluted sequentially with water and 50% ethanol. Peroxidases (91%) were extracted in 5.5-fold water extracts and 87% phenolics were extracted in 4.4-fold ethanol extracts. Purified peroxidases powder was yielded at 3.1 g (8.6 unit/mg) per kilogram stems by PEG6000/Na2SO4 aqueous two-phase purification from the water extracts (93.2% recovery), followed by ethanol precipitation and vacuum freeze-drying. The purified peroxidase had high activity in transforming tea catechins into theaflavins. Phenolics powder containing 43% phenolics and 27% flavonoids was yielded at 76.9 g per kilogram stems after vacuum-concentrating the ethanol extracts. This method can make valuable functional products using the sweet potato waste.
Designing Rashba–Dresselhaus effect in magnetic insulators
Authors: Kawano Masataka , Onose Yoshinori , Hotta Chisa 
Published: March 2019

AbstractOne of the major strategies to control magnetism in spintronics is to utilize the coupling between electron spin and its orbital motion. The Rashba and Dresselhaus spin–orbit couplings induce magnetic textures of band electrons called spin momentum locking, which produces a spin torque by the injection of electric current. However, joule heating had been a bottleneck for device applications. Here, we propose a theory to generate further rich spin textures in insulating antiferromagnets with broken spatial inversion symmetry (SIS), which is easily controlled by a small magnetic field. In antiferromagnets, the ordered moments host two species of magnons that serve as internal degrees of freedom in analogy with electron spins. The Dzyaloshinskii–Moriya interaction introduced by the SIS breaking couples the two-magnon-degrees of freedom with the magnon momentum. We present a systematic way to design such texture and to detect it via magnonic spin current for the realization of antiferromagnetic memory.
Investigation of the calcium-induced activation of the bacteriophage T5 peptidoglycan hydrolase promoting host cell lysis
Authors: Kovalenko Angelina O , Chernyshov Sergei V , Kutyshenko Victor P , Molochkov Nikolai V , Prokhorov Dmitry A , Odinokova Irina V , Mikoulinskaia Galina V 
Published: March 2019

AbstractPeptidoglycan hydrolase of bacteriophage T5 (EndoT5) is a Ca2+-dependent l-alanyl-d-glutamate peptidase, although the mode of Ca2+ binding and its physiological significance remain obscure. Site-directed mutagenesis was used to elucidate the role of the polar amino acids of the mobile loop of EndoT5 (111–130) in Ca2+ binding. The mutant proteins were purified to electrophoretic homogeneity, the overall structures were characterized by circular dichroism, and the calcium dissociation constants were determined via NMR spectroscopy. The data suggest that polar amino acids D113, N115, and S117 of EndoT5 are involved in the coordination of calcium ions by forming the core of the EF-like Ca2+-binding loop while the charged residues D122 and E123 of EndoT5 contribute to maintaining the loop net charge density. The results suggest that Ca2+ binding to the EndoT5 molecule could be essential for the stabilization of the long mobile loop in the catalytically active “open” conformation. The possible mechanism of Ca2+ regulation of EndoT5 activity during bacteriophage T5’s life cycle through the Ca2+ concentration difference between the cytoplasm and the periplasm of the host bacteria cell has been discussed. The study reveals valuable insight into the role of calcium in the regulation of phage-induced bacterial lysis.
Signalling circuits that direct early B-cell development
Authors: Petkau Georg , Turner Martin 
Published: March 2019

AbstractIn mammals, the B-cell lineage arises from pluripotent progenitors in the bone marrow. During their development, B-cells undergo lineage specification and commitment, followed by expansion and selection. These processes are mediated by regulated changes in gene expression programmes, rearrangements of immunoglobulin (Ig) genes, and well-timed rounds of proliferation and apoptosis. Many of these processes are initiated by environmental factors including cytokines, chemokines, and cell–cell contacts. Developing B-cells process these environmental cues into stage-specific functions via signalling pathways including the PI3K, MAPK, or JAK-STAT pathway. The cytokines FLT3-Ligand and c-Kit-Ligand are important for the early expansion of the B-cell precursors at different developmental stages and conditions. Interleukin 7 is essential for commitment to the B-cell lineage and for orchestrating the Ig recombination machinery. After rearrangement of the immunoglobulin heavy chain, proliferation and apoptosis, and thus selection, are mediated by the clonal pre-B-cell receptor, and, following light chain rearrangement, by the B-cell receptor.
Survival prediction of tuberous sclerosis complex gene variant in patients with advanced non-small-cell lung cancer treated with platinum doublet
Authors: Ryu Jeong-Seon , Lim Jun Hyeok , Kim Hyun-Jung , Kim Min Jeong , Park Mi Hwa , Kim Jung Soo 
Published: March 2019

Abstract
Tuberous sclerosis complex (TSC) 1 and 2 function as tumor suppressors by inactivating the mammalian target of rapamycin (mTOR) pathway. Although the effect of platinum on TSC function has been studied, associations between TSC gene variants and survival of cancer patients treated with platinum-based chemotherapy were not evaluated. Genetic variants of TSC1 and TSC2 were identified by next-generation sequencing and selected for further clinical evaluation based on predetermined criteria. Associations of the gene variants with treatment outcomes (progression-free survival, PFS; overall survival, OS) were evaluated in testing and validation sets of patients with advanced non-small-cell lung cancer (NSCLC). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the multivariable Cox model. The TSC1 Met322Thr (rs1073123) variant met the criteria for further analysis in testing and validation sets each containing 183 patients. The median PFS for the 366 patients was 4.9 months. Fifty-three patients (14.5%) had the TSC1 (Met322Thr or Thr322Thr) variant. TSC1 Met322Thr associated with longer PFS in the testing set (HR adjusted for age, gender, smoking habits, Eastern Cooperative Oncology Group performance status, histology, and stage [aHR] and 95% CI: 0.63 and 0.45–0.87, Cox P=0.009), and this was confirmed in the validation set (aHR and 95% CI: 0.58 and 0.36–0.93, Cox P=0.004). However, no association was found between the TSC1 gene variant and OS. These findings suggest that the TSC1 gene variant is an important predictive marker for platinum doublet chemotherapy outcomes in NSCLC patients.
Venus Express radio occultation observed by PRIDE
Authors: Bocanegra-Bahamón T. M. , Molera Calvés G. , Gurvits L. I. , Cimò G. , Dirkx D. , Duev D. A. , Pogrebenko S. V. , Rosenblatt P. , Limaye S. , Cui L. , Li P. , Kondo T. , Sekido M. , Mikhailov A. G. , Kharinov M. A. , Ipatov A. V. , Wang W. , Zheng W. , Ma M. , Lovell J. E. J. , McCallum J. N. 
Published: March 2019

Context. Radio occultation is a technique used to study planetary atmospheres by means of the refraction and absorption of a spacecraft carrier signal through the atmosphere of the celestial body of interest, as detected from a ground station on Earth. This technique is usually employed by the deep space tracking and communication facilities (e.g., NASA’s Deep Space Network (DSN), ESA’s Estrack).
Aims. We want to characterize the capabilities of the Planetary Radio Interferometry and Doppler Experiment (PRIDE) technique for radio occultation experiments, using radio telescopes equipped with Very Long Baseline Interferometry (VLBI) instrumentation.
Methods. We conducted a test with ESA’s Venus Express (VEX), to evaluate the performance of the PRIDE technique for this particular application. We explain in detail the data processing pipeline of radio occultation experiments with PRIDE, based on the collection of so-called open-loop Doppler data with VLBI stations, and perform an error propagation analysis of the technique.
Results. With the VEX test case and the corresponding error analysis, we have demonstrated that the PRIDE setup and processing pipeline is suited for radio occultation experiments of planetary bodies. The noise budget of the open-loop Doppler data collected with PRIDE indicated that the uncertainties in the derived density and temperature profiles remain within the range of uncertainties reported in previous Venus’ studies. Open-loop Doppler data can probe deeper layers of thick atmospheres, such as that of Venus, when compared to closed-loop Doppler data. Furthermore, PRIDE through the VLBI networks around the world, provides a wide coverage and range of large antenna dishes, that can be used for this type of experiments.
Stellar and substellar companions of nearby stars from Gaia DR2
Authors: Kervella Pierre , Arenou Frédéric , Mignard François , Thévenin Frédéric 
Published: March 2019

Context. The census of stellar and substellar companions of nearby stars is largely incomplete, in particular toward the low-mass brown dwarf and long-period exoplanets. It is, however, fundamentally important in the understanding of the stellar and planetary formation and evolution mechanisms. Nearby stars are particularly favorable targets for high precision astrometry.
Aims. We aim to characterize the presence of physical companions of stellar and substellar mass in orbit around nearby stars.
Methods. Orbiting secondary bodies influence the proper motion of their parent star through their gravitational reflex motion. Using the HIPPARCOS and Gaia’s second data release (GDR2) catalogs, we determined the long-term proper motion of the stars common to these two catalogs. We then searched for a proper motion anomaly (PMa) between the long-term proper motion vector and the GDR2 (or HIPPARCOS) measurements, indicative of the presence of a perturbing secondary object. We focussed our analysis on the 6741 nearby stars located within 50 pc, and we also present a catalog of the PMa for ≳99% of the HIPPARCOS catalog (≈117 000 stars).
Results. 30% of the stars studied present a PMa greater than 3σ. The PMa allows us to detect orbiting companions, or set stringent limits on their presence. We present a few illustrations of the PMa analysis to interesting targets. We set upper limits of 0.1−0.3 MJ to potential planets orbiting Proxima between 1 and 10 au (Porb = 3 to 100 years). We confirm that Proxima is gravitationally bound to α Cen. We recover the masses of the known companions of ϵ Eri, ϵ Ind, Ross 614 and β Pic. We also detect the signature of a possible planet of a few Jovian masses orbiting τ Ceti.
Conclusions. Based on only 22 months of data, the GDR2 has limitations. But its combination with the HIPPARCOS catalog results in very high accuracy PMa vectors, that already enable us to set valuable constraints on the binarity of nearby objects. The detection of tangential velocity anomalies at a median accuracy of σ(ΔvT) = 1.0 m s−1 per parsec of distance is already possible with the GDR2. This type of analysis opens the possibility to identify long period orbital companions otherwise inaccessible. For long orbital periods, Gaia’s complementarity to radial velocity and transit techniques (that are more sensitive to short orbital periods) already appears to be remarkably powerful.
Checkpoint-Inhibitoren: Die neue Immuntherapie bei gastrointestinalen Karzinomen
Authors: Moehler Markus , Foerster Friedrich 
Published: March 2019

ZusammenfassungDie Immuntherapie erfährt viel Aufmerksamkeit in der Krebsmedizin wegen beachtlicher therapeutischer Erfolge bei zahlreichen Tumorarten. Die zentrale Medikamentengruppe sind die Checkpoint-Inhibitoren (CI) – für ihre Entdeckung wurde 2018 der Nobelpreis für Medizin verliehen. Dieser Beitrag gibt einen Überblick über die bereits vorhandene Evidenz und den aktuellen Stellenwert von CI bei der Therapie gastrointestinaler Tumoren.
Effect of Homeopathic Medicines and a Nosode on Larvae of Cochliomyia hominivorax (Diptera: Calliphoridae)
Authors: de Barros Giuliano Pereira , Seugling Jaqueline , Bricarello Patrizia Ana 
Published: March 2019

Background Cochliomyia hominivorax is the major fly causing primary myiasis in livestock animals in Brazil; its larvae develop in the host's living tissues, causing mutilations, which can even lead to death. In conventional treatments of myiasis, chemo-synthetic insecticides have been employed directly on larvae present in the wounds. Homeopathy may represent a healthy and sustainable alternative both to prevent and to treat myiasis in animals and humans. The current study evaluated how the emergence of adult insects is affected by the use of the homeopathic medicines Sulfur 12cH and Pyrogenium 12cH, and the nosode produced from C. hominivorax larvae at potencies 8cH and 12cH, on third-stage larvae of a C. hominivorax colony.
Materials and Methods The homeopathic medicines and the nosodes were produced according to the Brazilian Homeopathic Pharmacopoeia. Control groups were distilled water, alcohol, no substance, and the organophosphate insecticide trichlorfon. For each group, 10 replicates were performed. Emergence rate of adult insects was evaluated by descriptive statistics followed by analysis of variance. Homogeneity of variances was verified by F-test and group means were compared with Tukey's test.
Results Mortality rates in control groups were 2.7% for 30% (v/v) alcohol, 4.3% for distilled water, 3.2% for no substance (p > 0.05). In the trichlorfon group, the mortality rate of larvae was 90.8%. For Sulfur 12cH, the mortality of larvae was 94.6%, and for Pyrogenium 12cH it was 98.6%. The latter three means were not statistically different from each other or from the mean found for the trichlorfon group. The mortality rates of larvae were 61.3% and 66.6% for nosode C. hominivorax 8cH and 12cH, respectively (p > 0.05).
Conclusions Results suggest that homeopathy could be used therapeutically to prevent and treat animals and humans with myiasis caused by C. hominivorax.