bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a feeder and serum-free culture system for human embryonic stem cells
Authors: Wang LiYun , Zhang RuiNa , Ma RongHua , Jia GongXue , Jian ShengYan , Zeng XiangHui , Xiong ZhengFang , Li BinYe , Li Chen , Lv ZhenZhen , Bai Xue 
Published: January 2020

SummaryStem cells are an immortal cell population capable of self-renewal; they are essential for human development and ageing and are a major focus of research in regenerative medicine. Despite considerable progress in differentiation of stem cellsin vitro, culture conditions require further optimization to maximize the potential for multicellular differentiation during expansion. The aim of this study was to develop a feeder-free, serum-free culture method for human embryonic stem cells (hESCs), to establish optimal conditions for hESC proliferation, and to determine the biological characteristics of the resulting hESCs. The H9 hESC line was cultured using a homemade serum-free, feeder-free culture system, and growth was observed. The expression of pluripotency proteins (OCT4, NANOG, SOX2, LIN28, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) in hESCs was determined by immunofluorescence and western blotting. The mRNA expression levels of genes encoding nestin, brachyury and α-fetoprotein in differentiated H9 cells were determined by RT-PCR. The newly developed culture system resulted in classical hESC colonies that were round or elliptical in shape, with clear and neat boundaries. The expression of pluripotency proteins was increased, and the genes encoding nestin, brachyury, and α-fetoprotein were expressed in H9 cells, suggesting that the cells maintainedin vitrodifferentiation capacity. Our culture system containing a unique set of components, with animal-derived substances, maintained the self-renewal potential and pluripotency of H9 cells for eight passages. Further optimization of this system may expand the clinical application of hESCs.
Cardiac functions and aortic elasticity in children with inflammatory bowel disease: effect of age at disease onset
Authors: Erolu Elif , Polat Esra 
Published: January 2020

AbstractAim:Childhood onset inflammatory bowel disease is more aggressive and has rapidly progressive clinical course than adult inflammatory bowel disease. Early-onset inflammatory bowel disease has more severe clinical progression as a subspecialised group of monogenic inflammatory bowel disease. We studied cardiac functions and aortic elasticity in children with early- and late-onset inflammatory bowel disease in remission period.Methods:Thirty-three paediatric patients were divided into subgroups according to age of disease onset (<10 and >10 years of age). Twenty-five healthy children were admitted as control group. M-Mode echocardiography and pulsed wave Doppler echocardiography were performed. Strain, distensibility, stiffness index of ascending, and abdominal aorta were evaluated.Results:Interventricular septum (mm) and left ventricular end-systolic diameter were higher (6.9 ± 1.2, 26.2 ± 4.6) in early-onset inflammatory bowel disease patients than control patients (6.1 ± 1.27, 22.7 ± 4.12) (p = 0.050, p = 0.050). Mitral E/E′ ratio and myocardial performance index were increased in inflammatory bowel disease and early-onset inflammatory bowel disease groups than control group (p = 0.046, p = 0.04; p = 0.023, p = 0.033). Diastolic functions were found to be impaired in inflammatory bowel disease and early-onset inflammatory bowel disease groups according to control group, while there was no difference between late-onset inflammatory bowel disease and control groups in terms of diastolic functions. Mitral E/A ratio was lower in inflammatory bowel disease patients and early-onset inflammatory bowel disease patients (1.46 ± 0.32, 1.4 ± 0.21) than control patients (1.70 ± 0.27) (p = 0.013, p = 0.004). Aortic elasticity did not differ between groups.Conclusion:Chronic low-grade inflammation has effects on left ventricular diameters and diastolic function in remission period. Aortic elasticity is not affected in our study groups.
Single-dose pharmacokinetics of amphetamine extended-release tablets compared with amphetamine extended-release oral suspension
Authors: Pardo Antonio , Kando Judith C. , King Thomas R. , Rafla Eman , Herman Barry K. 
Published: January 2020

AbstractObjectiveEvaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.MethodsHealthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.ResultsThirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.ConclusionsSingle doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.
Evidences of Plug Pressurization Enhancing Magma Fragmentation During the September 2016 Basaltic Eruption at Piton de la Fournaise (La Réunion Island, France)
Authors: Thivet Simon , Gurioli Lucia , Di Muro Andrea , Derrien Allan , Ferrazzini Valérie , Gouhier Mathieu , Coppola Diego , Galle Bo , Arellano Santiago 
Published: January 2020

AbstractIn September 2016, Piton de la Fournaise volcano, well known for its effusive and Hawaiian fountaining activity, produced, at the end of the eruption, an unusual phase of pulsating ash and bomb emission. Integration of geophysical data, with textural and petrological analysis of the samples, allowed us to constrain the main factors that controlled this sudden shift in activity, potentially dangerous for the tourist population that usually approach these “gentle” eruptive sites. Volcanic tremor, lava discharge rates, fountain heights, and SO2 emission changed rapidly during the eruption. Grain size and componentry of the tephra beds evolved from unimodal all along the sequence to bimodal on the last day of the activity, reflecting the contribution of both Hawaiian fountaining at the main vent (Vent A) and transient explosive activity at the second vent (Vent B). Hawaiian fountaining produced highly vesicular and almost microlite‐free tephra (golden pumice and fluidal scoria) while transient explosive activity emitted denser and crystal‐rich tephra (sideromelane and tachylite scoria) sometimes mingled with vesicular fragments. Permeability measurements on lapilli and bomb‐sized samples reveal that golden pumice and fluidal scoria were more gas‐permeable than the sideromelane and tachylite ones, while textural and chemical analyses of the ash support the hypothesis that these sideromelane and tachylite components were inherited from the subsurface crystallization of the initial golden pumice and fluidal scoria components. We thus suggest that Vent B accumulated a plug of degassed, cooled, and low‐permeable magma, which modulated overpressure pulses under the late input of ascending magma.
Changing Flow Paths Caused by Simultaneous Shearing and Fracturing Observed During Hydraulic Stimulation
Authors: Krietsch H. , Villiger L. , Doetsch J. , Gischig V. , Evans K. F. , Brixel B. , Jalali M. R. , Loew S. , Giardini D. , Amann F. 
Published: January 2020

AbstractWe monitored the seismohydromechanical rock mass response to high‐pressure fluid injection during a decameter‐scale hydraulic stimulation experiment in crystalline rock at the Grimsel Test Site, Switzerland. Time series recorded at two pressure monitoring locations show abrupt pressure increases that change in amplitude and appearance between subsequent stimulation cycles. Induced seismicity correlates with the propagation of one of these pressure fronts. Deformation data along the same shear zone shows permanent fracture dislocation preceded by strong transient fracture opening. We interpret these observations as nonlinear pressure diffusion along flow channels that reorganize in response to hydromechanical effects during stimulation. Combining these observations with the in situ stress field estimated before stimulation, we argue that the underlying hydromechanical processes involve mixed‐mode stimulation with both Mode I and II/III fracture dislocation.
Detections of Water Vapor Increase Over the North Polar Troughs on Mars as Observed by CRISM
Authors: Khayat Alain SJ. , Smith Michael D. , Guzewich Scott D. 
Published: January 2020

AbstractThe Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) onboard the Mars Reconnaissance Orbiter has been observing the north polar layered deposits (NPLD) of Mars. Polar wind circulations are instrumental in shaping the NPLD. In particular, the downslope (katabatic) flows help carve the spiral‐shaped geological depressions, known as the polar troughs, and appropriate environmental conditions develop katabatic jumps that favor substantial water abundance changes over the troughs. Utilizing CRISM retrievals, we report the first observational evidence of the sharp increase in the water vapor abundance over polar troughs on Mars at high resolution (~320 m). This has a direct influence on the dynamic evolution of ice migration in the northern polar cap, the major source of atmospheric water on Mars.
The Potential Impact of Nuclear Conflict on Ocean Acidification
Authors: Lovenduski Nicole S. , Harrison Cheryl S. , Olivarez Holly , Bardeen Charles G. , Toon Owen B. , Coupe Joshua , Robock Alan , Rohr Tyler , Stevenson Samantha 
Published: January 2020

AbstractWe demonstrate that the global cooling resulting from a range of nuclear conflict scenarios would temporarily increase the pH in the surface ocean by up to 0.06 units over a 5‐year period, briefly alleviating the decline in pH associated with ocean acidification. Conversely, the global cooling dissolves atmospheric carbon into the upper ocean, driving a 0.1 to 0.3 unit decrease in the aragonite saturation state (
) that persists for
10 years. The peak anomaly in pH occurs 2 years post conflict, while the
anomaly peaks 4‐ to 5‐years post conflict. The decrease in
would exacerbate a primary threat of ocean acidification: the inability of marine calcifying organisms to maintain their shells/skeletons in a corrosive environment. Our results are based on sensitivity simulations conducted with a state‐of‐the‐art Earth system model integrated under various black carbon (soot) external forcings. Our findings suggest that regional nuclear conflict may have ramifications for global ocean acidification.
Evidence for auxiliary anaerobic metabolism in obligately aerobic Zetaproteobacteria
Authors: Jain Abhiney , Gralnick Jeffrey A 
Published: January 2020

Abstract
Zetaproteobacteria are obligate chemolithoautotrophs that oxidize Fe(II) as an electron and energy source, and play significant roles in nutrient cycling and primary production in the marine biosphere. Zetaproteobacteria thrive under microoxic conditions near oxic–anoxic interfaces, where they catalyze Fe(II) oxidation faster than the abiotic reaction with oxygen. Neutrophilic Fe(II) oxidizing bacteria produce copious amounts of insoluble iron oxyhydroxides as a by-product of their metabolism. Oxygen consumption by aerobic respiration and formation of iron oxyhydroxides at oxic–anoxic interfaces can result in periods of oxygen limitation for bacterial cells. Under laboratory conditions, all Zetaproteobacteria isolates have been shown to strictly require oxygen as an electron acceptor for growth, and anaerobic metabolism has not been observed. However, genomic analyses indicate a range of potential anaerobic pathways present in Zetaproteobacteria. Heterologous expression of proteins from Mariprofundus ferrooxydans PV-1, including pyruvate formate lyase and acetate kinase, further support a capacity for anaerobic metabolism. Here we define auxiliary anaerobic metabolism as a mechanism to provide maintenance energy to cells and suggest that it provides a survival advantage to Zetaproteobacteria in environments with fluctuating oxygen availability.
L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction
Authors: Chellaiah Meenakshi A. , Moorer Megan C. , Majumdar Sunipa , Aljohani Hanan , Morley Sharon C. , Yingling Vanessa , Stains Joseph P. 
Published: January 2020

AbstractBone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones (NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Transduction of TAT-fused full-length L-plastin peptide into osteoclasts from L-plastin knockout mice rescued the formation of nascent sealing zones and sealing rings in a time-dependent manner. This response was not observed with mutated full-length L-plastin (Ser-5 and -7 to Ala-5 and -7) peptide. In contrast to the observed defect in the NSZ, L-plastin deficiency did not affect podosome formation or adhesion of osteoclasts in vitro or in vivo. Histomorphometry analyses in 8- and 12-week-old female L-plastin knockout mice demonstrated a decrease in eroded perimeters and an increase in trabecular bone density, without a change in bone formation by osteoblasts. This decrease in eroded perimeters supports that osteoclast function is attenuated in L-plastin knockouts. Micro-CT analyses confirmed a marked increase in trabecular bone mass. In conclusion, female L-plastin knockout mice had increased trabecular bone density due to impaired bone resorption by osteoclasts. L-plastin could be a potential target for therapeutic interventions to treat trabecular bone loss.
Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer
Authors: Ma Jing , Ramachandran Mohanraj , Jin Chuan , Quijano-Rubio Clara , Martikainen Miika , Yu Di , Essand Magnus 
Published: January 2020

AbstractOncolytic viruses have the potential to induce immunogenic cell death (ICD) that may provoke potent and long-lasting anti-cancer immunity. Here we aimed to characterize the ICD-inducing ability of wild-type Adenovirus (Ad), Semliki Forest virus (SFV) and Vaccinia virus (VV). We did so by investigating the cell death and immune-activating properties of virus-killed tumor cells. Ad-infection of tumor cells primarily activates autophagy, but also activate events of necroptotic and pyroptotic cell death. SFV infection on the other hand primarily activates immunogenic apoptosis while VV activates necroptosis. All viruses mediated lysis of tumor cells leading to the release of danger-associated molecular patterns, triggering of phagocytosis and maturation of dendritic cells (DCs). However, only SFV-infected tumor cells triggered significant T helper type 1 (Th1)-cytokine release by DCs and induced antigen-specific T-cell activation. Our results elucidate cell death processes activated upon Ad, SFV, and VV infection and their potential to induce T cell-mediated anti-tumor immune responses. This knowledge provides important insight for the choice and design of therapeutically successful virus-based immunotherapies.
TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-β1/Smads and activating P53 signaling pathways
Authors: Gao Lei , Wang Li-you , Liu Zhi-qiang , Jiang Dan , Wu Shi-yong , Guo Yu-qian , Tao Hong-mei , Sun Min , You Lin-na , Qin Shu , Cheng Xiao-cheng , Xie Jun-shi , Chang Guang-lei , Zhang Dong-ying 
Published: January 2020

AbstractTissue nonspecific alkaline phosphatase (TNAP) is expressed widely in different tissues, modulating functions of metabolism and inflammation. However, the effect of TNAP on cardiac fibrosis remains controversial and needs to be further studied. The present study aims to investigate the role of TNAP on myocardial infarction (MI)-induced fibrosis and its mechanism. TNAP was upregulated in patients with MI, both in serum and injured hearts, and predicted in-hospital mortality. TNAP was also significantly upregulated after MI in rats, mostly in the border zone of the infarcted hearts combined with collagen synthesis. Administration of TNAP inhibitor, tetramisole, markedly improved cardiac function and fibrosis after MI. In the primary cultures of neonatal rat cardiac fibroblasts (CFs), TNAP inhibition significantly attenuated migration, differentiation, and expression of collagen-related genes. The TGF-β1/Smads signaling suppression, and p-AMPK and p53 upregulation were involved in the process. When p53 inhibitor was administered, the antifibrotic effect of TNAP inhibition can be blocked. This study provides a direct evidence that inhibition of TNAP might be a novel regulator in cardiac fibrosis and exert an antifibrotic effect mainly through AMPK-TGF-β1/Smads and p53 signals.
RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer
Authors: Han Mingli , Hu Jianguo , Lu Pengwei , Cao Hui , Yu Chao , Li Xiangke , Qian Xueke , Yang Xue , Yang Yunqing , Han Na , Dou Dongwei , Zhang Fan , Ye Mulin , Yang Changcheng , Gu Yuanting , Dong Huaying 
Published: January 2020

AbstractTrastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain- or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.
The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus
Authors: Furukawa Takanori , van Rhijn Norman , Fraczek Marcin , Gsaller Fabio , Davies Emma , Carr Paul , Gago Sara , Fortune-Grant Rachael , Rahman Sayema , Gilsenan Jane Mabey , Houlder Emma , Kowalski Caitlin H. , Raj Shriya , Paul Sanjoy , Cook Peter , Parker Josie E. , Kelly Steve , Cramer Robert A. , Latgé Jean-Paul , Moye-Rowley Scott , Bignell Elaine , Bowyer Paul , Bromley Michael J. 
Published: January 2020

AbstractThe frequency of antifungal resistance, particularly to the azole class of ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant isolates are exceptionally low. Beyond modification of the drug target, our understanding of the molecular basis of azole resistance in the fungal pathogen Aspergillus fumigatus is limited. We reasoned that clinically relevant antifungal resistance could derive from transcriptional rewiring, promoting drug resistance without concomitant reductions in pathogenicity. Here we report a genome-wide annotation of transcriptional regulators in A. fumigatus and construction of a library of 484 transcription factor null mutants. We identify 12 regulators that have a demonstrable role in itraconazole susceptibility and show that loss of the negative cofactor 2 complex leads to resistance, not only to the azoles but also the salvage therapeutics amphotericin B and terbinafine without significantly affecting pathogenicity.
Diameter-independent skyrmion Hall angle observed in chiral magnetic multilayers
Authors: Zeissler Katharina , Finizio Simone , Barton Craig , Huxtable Alexandra J. , Massey Jamie , Raabe Jörg , Sadovnikov Alexandr V. , Nikitov Sergey A. , Brearton Richard , Hesjedal Thorsten , van der Laan Gerrit , Rosamond Mark C. , Linfield Edmund H. , Burnell Gavin , Marrows Christopher H. 
Published: January 2020

AbstractMagnetic skyrmions are topologically non-trivial nanoscale objects. Their topology, which originates in their chiral domain wall winding, governs their unique response to a motion-inducing force. When subjected to an electrical current, the chiral winding of the spin texture leads to a deflection of the skyrmion trajectory, characterised by an angle with respect to the applied force direction. This skyrmion Hall angle is predicted to be skyrmion diameter-dependent. In contrast, our experimental study finds that the skyrmion Hall angle is diameter-independent for skyrmions with diameters ranging from 35 to 825 nm. At an average velocity of 6 ± 1 ms−1, the average skyrmion Hall angle was measured to be 9° ± 2°. In fact, the skyrmion dynamics is dominated by the local energy landscape such as materials defects and the local magnetic configuration.