bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity of human pluripotent stem cells to insulin precipitation induced by peristaltic pump-based medium circulation: considerations on process development
Authors: Massai Diana , Bolesani Emiliano , Diaz Diana Robles , Kropp Christina , Kempf Henning , Halloin Caroline , Martin Ulrich , Braniste Tudor , Isu Giuseppe , Harms Vanessa , Morbiducci Umberto , Dräger Gerald , Zweigerdt Robert 
Published: June 2017

AbstractControlled large-scale production of human pluripotent stem cells (hPSCs) is indispensable for their envisioned clinical translation. Aiming at advanced process development in suspension culture, the sensitivity of hPSC media to continuous peristaltic pump-based circulation, a well-established technology extensively used in hydraulically-driven bioreactors, was investigated. Unexpectedly, conditioning of low protein media (i.e. E8 and TeSR-E8) in a peristaltic pump circuit induced severe viability loss of hPSCs cultured as aggregates in suspension. Optical, biochemical, and cytological analyses of the media revealed that the applied circulation mode resulted in the reduction of the growth hormone insulin by precipitation of micro-sized particles. Notably, in contrast to insulin depletion, individual withdrawal of other medium protein components (i.e. bFGF, TGFβ1 or transferrin) provoked minor reduction of hPSC viability, if any. Supplementation of the surfactant glycerol or the use of the insulin analogue Aspart did not overcome the issue of insulin precipitation. In contrast, the presence of bovine or human serum albumin (BSA or HSA, respectively) stabilized insulin rescuing its content, possibly by acting as molecular chaperone-like protein, ultimately supporting hPSC maintenance. This study highlights the potential and the requirement of media optimization for automated hPSC processing and has broad implications on media development and bioreactor-based technologies.
Outstanding compressive creep strength in Cr/Ir-codoped (Mo0.85Nb0.15)Si2 crystals with the unique cross-lamellar microstructure
Authors: Hagihara Koji , Ikenishi Takaaki , Araki Haruka , Nakano Takayoshi 
Published: June 2017

AbstractA (Mo0.85Nb0.15)Si2 crystal with an oriented, lamellar, C40/C11b two-phase microstructure is a promising ultrahigh-temperature (UHT) structural material, but its low room-temperature fracture toughness and low high-temperature strength prevent its practical application. As a possibility to overcome these problems, we first found a development of unique “cross-lamellar microstructure”, by the cooping of Cr and Ir. The cross-lamellar microstructure consists of a rod-like C11b-phase grains that extend along a direction perpendicular to the lamellar interface in addition to the C40/C11b fine lamellae. In this study, the effectiveness of the cross-lamellar microstructure for improving the high-temperature creep deformation property, being the most essential for UHT materials, was examined by using the oriented crystals. The creep rate significantly reduced along a loading orientation parallel to the lamellar interface. Furthermore, the degradation in creep strength for other loading orientation that is not parallel to the lamellar interface, which has been a serious problem up to now, was also suppressed. The results demonstrated that the simultaneous improvement of high-temperature creep strength and room temperature fracture toughness can be first accomplished by the development of unique cross-lamellar microstructure, which opens a potential avenue for the development of novel UHT materials as alternatives to existing Ni-based superalloys.
Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice
Authors: Ye Lei , Kan Fangming , Yan Tao , Cao Jiaqi , Zhang Leiliang , Wu Zhijian , Li Wuping 
Published: June 2017

AbstractThe hepatitis B virus (HBV) causes acute and chronic liver infection, which may lead to liver cirrhosis and hepatocellular carcinoma. Current treatments including interferons and nucleotide analogs, have limited therapeutic effects, underscoring the need to identify effective therapeutic options to inhibit HBV replication and prevent complications. Previous animal models mimicking chronic HBV infection do not faithfully reflect disease progression in humans. Here, we used our established HBV-persistent mouse line with liver fibrosis to evaluate the efficacy of novel therapies. The combination of two short hairpin RNAs (dual-shRNA) against different coding regions of HBV delivered by a self-complementary AAV vector showed better antiviral effects than single shRNA both in vitro and in HBV-persistent mice. The dual-shRNA also exhibited stronger antifibrotic activity in vivo. Vector carrying shRNA against TGF-β, though did not inhibit HBV replication alone, enhanced the antiviral and antifibrotic activities of single and dual HBV shRNAs. Co-administration of TGF-β shRNA and HBV dual-shRNA decreased HBV DNA, HBV RNA, HBsAg, HBeAg, and liver fibrosis markers in serum and tissues, and improved liver morphology more effectively than single treatments. Our results suggest that the combination of shRNAs against HBV and TGF-β could be developed into a viable treatment for human HBV infection.
Microbial Antigens Stimulate Metalloprotease-7 Secretion in Human B-Lymphocytes Using mTOR-Dependent and Independent Pathways
Authors: Ali Mohamed F. , Dasari Harika , Van Keulen Virginia P. , Cornec Divi , Vasmatzis George , Peikert Tobias , Carmona Eva M. 
Published: June 2017

AbstractMetalloproteinases (MMPs) contribute to tissue remodeling and acute inflammation not only by degrading extracellular matrix proteins but also by controlling the influx of chemokines through the regulation and shedding of syndecans. B-lymphocytes, in addition to their well-known function as antibody producing cells, participate in the innate immune response by secreting inflammatory cytokines and chemokines. However, there is little information about the role of B-lymphocytes in the regulation of MMPs; consequently, herein we investigated whether activated human circulating B-lymphocytes contributed to the secretion of MMPs. We demonstrate that B-lymphocytes activated by un-methylated CpG motifs, found in bacterial DNA, and β-glucans, found in the cell wall of fungi, both induced MMP-7. Interestingly, while CpG-stimulated cells activated the mTOR pathwayviaTLR9 receptor to induced MMP-7, β-glucan-stimulated cells were mTOR-independent and used Dectin-1 receptor. B-lymphocytes did not seem to have a major role in the secretion of tissue inhibitors of metalloproteinases (TIMPs). However, secreted MMP-7 participated in the shedding of Syndecan-4 from the surface of B-lymphocytes. In conclusion, circulating human B-lymphocytes contribute to the regulation of the innate immune system by participating in the secretion of MMP-7 which in turn is important for the shedding of Syndecan-4 in response to infectious stimuli.
Enhancing KCC2 function counteracts morphine-induced hyperalgesia
Authors: Ferrini Francesco , Lorenzo Louis-Etienne , Godin Antoine G. , Quang Miorie Le , De Koninck Yves 
Published: June 2017

AbstractMorphine-induced hyperalgesia (MIH) is a severe adverse effect accompanying repeated morphine treatment, causing a paradoxical decrease in nociceptive threshold. Previous reports associated MIH with a decreased expression of the Cl− extruder KCC2 in the superficial dorsal horn (SDH) of the spinal cord, weakening spinal GABAA/glycine-mediated postsynaptic inhibition. Here, we tested whether the administration of small molecules enhancing KCC2, CLP257 and its pro-drug CLP290, may counteract MIH. MIH was typically expressed within 6–8 days of morphine treatment. Morphine-treated rats exhibited decreased withdrawal threshold to mechanical stimulation and increased vocalizing behavior to subcutaneous injections. Chloride extrusion was impaired in SDH neurons measured as a depolarizing shift in EGABA under Cl− load. Delivering CLP257 to spinal cord slices obtained from morphine-treated rats was sufficient to restore Cl− extrusion capacity in SDH neurons. In vivo co-treatment with morphine and oral CLP290 prevented membrane KCC2 downregulation in SDH neurons. Concurrently, co-treatment with CLP290 significantly mitigated MIH and acute administration of CLP257 in established MIH restored normal nociceptive behavior. Our data indicate that enhancing KCC2 activity is a viable therapeutic approach for counteracting MIH. Chloride extrusion enhancers may represent an effective co-adjuvant therapy to improve morphine analgesia by preventing and reversing MIH.
Shape and Composition Control of Monodisperse Hybrid Pt-CoO Nanocrystals by Controlling the Reaction Kinetics with Additives
Authors: Woo Hyunje , Kim Eunji , Kim Jun-Hyuk , Yun Su-Won , Park Ji Chan , Kim Yong-Tae , Park Kang Hyun 
Published: June 2017

AbstractHere, we report the effect of Fe(CO)5 additives in the synthesis of branched Pt-CoO nanowires (NWs) and core@shell concave nanocubes (NCs), in a one-pot system. Key to the success of this synthesis is control over the shape of the Pt seeds by controlling the quantity of Fe(CO)5 additive. In the absence of Fe(CO)5, branched Pt-CoO NWs were synthesized through the attachment of small Pt seed particles, followed by the growth of CoO by deposition. On the other hand, Pt@CoO concave NCs were obtained in the presence of Fe(CO)5 because of the stronger adsorption of Co on the Pt (100) surfaces than on the closely packed (111) surfaces. Also, various other conditions including the control of reducing agents, precursor concentrations, and stabilizing agents, were used to verify the effects of reaction kinetics on the synthesis of Pt-CoO nanoparticles. Compared to Pt/graphene oxide (GO) catalyst, branched Pt-CoO NWs supported on GO showed enhanced specific activity toward the oxygen reduction reaction (ORR).
Increase in predation risk and trophic level induced by nocturnal visits of piscivorous fishes in a temperate seagrass bed
Authors: Shoji Jun , Mitamura Hiromichi , Ichikawa Kotaro , Kinoshita Hikari , Arai Nobuaki 
Published: June 2017

AbstractThe majority of surveys on food webs of aquatic ecosystems have been conducted during the day owning to difficulties in sampling animals at night. In this study, to examine diurnal changes in predator-prey interactions in a temperate seagrassZostera marinabed, a quantitative day/night survey of fish, the dominant animal community, coupled with acoustic telemetry of their predators, was conducted. The number of species, abundance, and biomass of piscivorous predators and mean trophic level during the night were significantly higher than those in the day in all seasons. Analysis of the stomach contents of 182 piscivorous predators showed that no fish predation occurred during the day whereas predation occurred during the night in winter, spring, and summer. Acoustic telemetry demonstrated nocturnal visits by dominant piscivorous fish species (rockfishes and conger eel) to the seagrass bed. We conclude that the nocturnal visits by piscivorous fishes increased the predation risk and trophic level in the fish nursery. The ecological functions of seagrass beds should be reevaluated accounting for day/night changes in food webs; these areas serve as nurseries for juvenile and small-sized fishes during the day and as foraging grounds for predators during the night.
Drug-Repositioning Screening for Keap1-Nrf2 Binding Inhibitors using Fluorescence Correlation Spectroscopy
Authors: Yoshizaki Yuki , Mori Takayasu , Ishigami-Yuasa Mari , Kikuchi Eriko , Takahashi Daiei , Zeniya Moko , Nomura Naohiro , Mori Yutaro , Araki Yuya , Ando Fumiaki , Mandai Shintaro , Kasagi Yuri , Arai Yohei , Sasaki Emi , Yoshida Sayaka , Kagechika Hiroyuki , Rai Tatemitsu , Uchida Shinichi , Sohara Eisei 
Published: June 2017

AbstractThe Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. The Cul3/Keap1 E3 ubiquitin ligase complex interacts with Nrf2, leading to Nrf2 ubiquitination and degradation. In this study, we focused on the disruption of the Keap1-Nrf2 interaction to upregulate Nrf2 expression and the transcription of ARE-controlled cytoprotective oxidative stress response enzymes, such as HO-1. We completed a drug-repositioning screening for inhibitors of Keap1-Nrf2 protein-protein interactions using a newly established fluorescence correlation spectroscopy (FCS) screening system. The binding reaction between Nrf2 and Keap1 was successfully detected with a KD of 2.6 μM using our FCS system. The initial screening of 1,633 drugs resulted in 12 candidate drugs. Among them, 2 drugs significantly increased Nrf2 protein levels in HepG2 cells. These two promising drugs also upregulated ARE gene promoter activity and increased HO-1 mRNA expression, which confirms their ability to dissociate Nrf2 and Keap1. Thus, drug-repositioning screening for Keap1-Nrf2 binding inhibitors using FCS enabled us to find two promising known drugs that can induce the activation of the Nrf2-ARE pathway.
High efficacy in vitro selection procedure for generating transgenic parasites of Plasmodium berghei using an antibiotic toxic to rodent hosts
Authors: Soga Akira , Bando Hironori , Ko-ketsu Mami , Masuda-Suganuma Hirono , Kawazu Shin-ichiro , Fukumoto Shinya 
Published: June 2017

AbstractThe malaria parasite Plasmodium berghei is one of the main rodent malaria models. A shortcoming of this model parasite is its low flexibility in genetic manipulation. As this parasite cannot be continuously propagated in cell cultures, in vivo drug selection procedures are necessary to isolate genetic mutants. Drugs harmful to rodents therefore cannot be used for drug selection, which restricts the range of genetic manipulation. In this study, we addressed this problem by establishing a novel in vitro culture drug selection method, which we used in combination with other established methods to successfully isolate genetically manipulated parasites. The target mutants were enriched to the desired level within two weeks. We show that our system can also be used for sequential genetic manipulation of parasites carrying the traditionally used selection markers, demonstrate the procedure’s versatility, and show its use in isolating specific genetically manipulated parasites. This novel in vitro selection method increases the number of available selection markers, allowing more extensive genetic manipulation in malaria parasite research.
Late-onset Circulatory Collapse and Continuous Positive Airway Pressure are Useful Predictors of Treatment-requiring Retinopathy of Prematurity: A 9-year Retrospective Analysis
Authors: Arima Mitsuru , Tsukamoto Shoko , Fujiwara Kohta , Murayama Miwa , Fujikawa Kanako , Sonoda Koh-Hei 
Published: June 2017

AbstractsVisual loss caused by retinopathy of prematurity (ROP) will be prevented if treatment-requiring ROP (TR-ROP) can be predicted. In this retrospective study including 418 infants with ≤32 weeks of gestational age (GA) and/or ≤1500 grams of birthweight, we attempted to identify useful predictors. We also examined the efficiency of significant predictors compared with existing predictive models, ROPScore and CHOP model. Multivariable logistic regression analyses supported the following factors were useful for predicting TR-ROP from all infants and infants with any ROP: GA (odds ratio [OR], 0.47 and 0.48), history of late-onset circulatory collapse (LCC) (OR, 2.76 and 2.44) and use of continuous positive airway pressure (CPAP) at 35 weeks of postmenstrual age (OR, 3.78 and 4.50). The comparison of areas under receiver operating characteristic curves indicated the combination of LCC, CPAP and ROPScore was better than ROPScore to predict TR-ROP from all infants and infants with any ROP (P = 0.007 and 0.02) and the combination of LCC, CPAP and CHOP model was also better than CHOP model to predict TR-ROP from all infants and infants with any ROP (P = 0.01 and 0.02). Our results suggested infants with a history of LCC and a long CPAP support have a high incidence of TR-ROP.
Thioesterase YbgC affects motility by modulating c-di-GMP levels in Shewanella oneidensis
Authors: Gao Tong , Meng Qiu , Gao Haichun 
Published: June 2017

AbstractBecause of ubiquity of thioesters, thioesterases play a critical role in metabolism, membrane biosynthesis, signal transduction, and gene regulation. In many bacteria, YbgC is such an enzyme, whose coding gene mostly resides in the tol-pal cluster. Although all other proteins encoded in the tol-pal cluster are clearly involved in maintaining cell envelope integrity and cell division, little is known about the physiological role of YbgC. In this study, we identify in Shewanella oneidensis, a γ-proteobacterium used as a research model for environmental microbes, YbgC as a motility regulator. The loss of YbgC results in enhanced motility, which is likely due to the increased rotation rate of the flagellum. The regulatory function of YbgC requires its thioesterase activity but could not be replaced by YbgC homologues of other bacteria. We further show that the regulation of YbgC is mediated by the second message c-di-GMP.
Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit
Authors: Liu Xinghua , Zeng Kuan , Li Mengzhu , Wang Qun , Liu Rong , Zhang Bin , Wang Jian-Zhi , Shu Xiji , Wang Xiaochuan 
Published: June 2017

AbstractIntracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer’s disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechanism by which mutant P301L hTau leads to dementia is not fully elucidated. Here, we studied the effects of P301L hTau transduction in the medial EC (MEC) of mice on tau phosphorylation and accumulation, and cognitive deficit. We found that the exogenous mutant tau protein was restricted in MEC without spreading to other brain regions at one month after transduction. Interestingly, expression of the mutant tau in MEC induces endogenous tau hyperphosphorylation and accumulation in hippocampus and cortex, and inhibits neuronal activity with attenuated PP-DG synapse plasticity, leading to hippocampus-dependent memory deficit with intact olfactory function. These findings suggest a novel neuropathological mechanism of early AD, which is initiated by tau accumulation in MEC, and demonstrate a tau pathological model of early stage AD.
Full-time response of starch subjected to microwave heating
Authors: Fan Daming , Wang Liyun , Zhang Nana , Xiong Lei , Huang Luelue , Zhao Jianxin , Wang Mingfu , Zhang Hao 
Published: June 2017

AbstractThe effect of non-ionizing microwave radiation on starch is due to a gelatinization temperature range that changes starch structure and properties. However, the changes in starch upon microwave heating are observable throughout the heating process. We compared the effects on starch heating by microwaves to the effects by rapid and regular conventional heating. Our results show that microwave heating promotes the rapid rearrangement of starch molecules at low temperatures; starch showed a stable dielectric response and a high dielectric constant. Microwave heating changed the Cole-Cole curve and the polarization of starch suspension at low temperatures. A marked transition at 2.45 GHz resulted in a double-polarization phenomenon. At temperatures below gelatinization, microwave-induced dielectric rearrangement and changes in the polarization characteristics of starch suspensions reduced the absorption properties; at temperatures above gelatinization, these characteristics became consistent with conventional heating. Throughout the heating process, microwaves change the electrical response and polarization characteristics of the starch at low temperatures, but on the macro level, there is no enhancement of the material’s microwave absorption properties. In contrast, with the warming process, the starch exhibited a “blocking effect”, and the absorption properties of the starch quickly returned to the level observed in conductive heating after gelatinization.
Modelled responses of the Kalahari Desert to 21st century climate and land use change
Authors: Mayaud Jerome R. , Bailey Richard M. , Wiggs Giles F. S. 
Published: June 2017

AbstractDrylands are home to over 2 billion people globally, many of whom use the land for agricultural and pastoral activities. These vulnerable livelihoods could be disrupted if desert dunefields become more active in response to climate and land use change. Despite increasing knowledge about the role that wind, moisture availability and vegetation cover play in shaping dryland landscapes, relatively little is known about how drylands might respond to climatic and population pressures over the 21stcentury. Here we use a newly developed numerical model, which fully couples vegetation and sediment-transport dynamics, to simulate potential landscape evolution at three locations in the Kalahari Desert, under two future emissions scenarios: stabilising (RCP 4.5) and high (RCP 8.5). Our simulations suggest that whilst our study sites will experience some climatically-induced landscape change, the impacts of climate change alone on vegetation cover and sediment mobility may be relatively small. However, human activity could strongly exacerbate certain landscape trajectories. Fire frequency has a primary impact on vegetation cover, and, together with grazing pressure, plays a significant role in modulating shrub encroachment and ensuing land degradation processes. Appropriate land management strategies must be implemented across the Kalahari Desert to avoid severe environmental and socio-economic consequences over the coming decades.
Identification of a flavonoid isolated from plum (Prunus domestica) as a potent inhibitor of Hepatitis C virus entry
Authors: Bose Mihika , Kamra Mohini , Mullick Ranajoy , Bhattacharya Santanu , Das Saumitra , Karande Anjali A. 
Published: June 2017

AbstractHepatitis C virus (HCV) infection is a major cause of chronic liver diseases that often requires liver transplantation. The standard therapies are limited by severe side effects, resistance development, high expense and in a substantial proportion of cases, fail to clear the infection which bespeak the need for development of well-tolerated antivirals. Since most of the drug development strategies target the replication stage of viral lifecycle, the identification of entry inhibitors might be crucial especially in case of liver-transplant recipients. In the present study we have evaluated fruits which are known for their hepatoprotective effects in order to screen for entry inhibitors. We report the identification of a flavonoid, rutin, isolated from Prunus domestica as a new HCV entry inhibitor. Characterization and confirmation of the chemical structure was done by LC-ESI-MS, NMR and IR spectral analyses. Rutin significantly inhibited HCV-LP binding to hepatoma cells and inhibited cell-culture derived HCV (HCVcc) entry into hepatoma cells. Importantly, rutin was found to be non-toxic to hepatoma cells. Furthermore, rutin inhibits the early entry stage of HCV lifecycle possibly by directly acting on the viral particle. In conclusion, rutin is a promising candidate for development of anti-HCV therapeutics in the management of HCV infection.