bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase
Authors: Pein Helmut , Ville Alexia , Pace Simona , Temml Veronika , Garscha Ulrike , Raasch Martin , Alsabil Khaled , Viault Guillaume , Dinh Chau-Phi , Guilet David , Troisi Fabiana , Neukirch Konstantin , König Stefanie , Bilancia Rosella , Waltenberger Birgit , Stuppner Hermann , Wallert Maria , Lorkowski Stefan , Weinigel Christina , Rummler Silke , Birringer Marc , Roviezzo Fiorentina , Sautebin Lidia , Helesbeux Jean-Jacques , Séraphin Denis , Mosig Alexander S. , Schuster Daniela , Rossi Antonietta , Richomme Pascal , Werz Oliver , Koeberle Andreas
Published: September 2018

Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human vitamin E metabolites, that long-chain ω-carboxylates are potent allosteric inhibitors of 5-lipoxygenase, a key enzyme in the biosynthesis of chemoattractant and vasoactive leukotrienes. 13-((2R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13′-COOH) can be synthesized from α-tocopherol in a human liver-on-chip, and is detected in human and mouse plasma at concentrations (8–49 nM) that inhibit 5-lipoxygenase in human leukocytes. α-T-13′-COOH accumulates in immune cells and inflamed murine exudates, selectively inhibits the biosynthesis of 5-lipoxygenase-derived lipid mediators in vitro and in vivo, and efficiently suppresses inflammation and bronchial hyper-reactivity in mouse models of peritonitis and asthma. Together, our data suggest that the immune regulatory and anti-inflammatory functions of α-tocopherol depend on its endogenous metabolite α-T-13′-COOH, potentially through inhibiting 5-lipoxygenase in immune cells.
Author Correction: Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression
Authors: Zhang Lingdi , Zhou Hengbo , Li Xueni , Vartuli Rebecca L. , Rowse Michael , Xing Yongna , Rudra Pratyaydipta , Ghosh Debashis , Zhao Rui , Ford Heide L.
Published: September 2018

In the original version of this Article, the title of the legend to Fig. 7 incorrectly read ‘Knockdown of B55α increases breast cancer metastasis’ instead of ‘Knockdown of B55α decreases breast cancer metastasis’. This has now been corrected in both the PDF and HTML versions of the Article.
Female mice lacking Ftx lncRNA exhibit impaired X-chromosome inactivation and a microphthalmia-like phenotype
Authors: Hosoi Yusuke , Soma Miki , Shiura Hirosuke , Sado Takashi , Hasuwa Hidetoshi , Abe Kuniya , Kohda Takashi , Ishino Fumitoshi , Kobayashi Shin
Published: September 2018

X-chromosome inactivation (XCI) is an essential epigenetic process in female mammalian development. Although cell-based studies suggest the potential importance of the Ftx long non-protein-coding RNA (lncRNA) in XCI, its physiological roles in vivo remain unclear. Here we show that targeted deletion of X-linked mouse Ftx lncRNA causes eye abnormalities resembling human microphthalmia in a subset of females but rarely in males. This inheritance pattern cannot be explained by X-linked dominant or recessive inheritance, where males typically show a more severe phenotype than females. In Ftx-deficient mice, some X-linked genes remain active on the inactive X, suggesting that defects in random XCI in somatic cells cause a substantially female-specific phenotype. The expression level of Xist, a master regulator of XCI, is diminished in females homozygous or heterozygous for Ftx deficiency. We propose that loss-of-Ftx lncRNA abolishes gene silencing on the inactive X chromosome, leading to a female microphthalmia-like phenotype.
Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a transmission blocking antibody
Authors: Lennartz Frank , Brod Florian , Dabbs Rebecca , Miura Kazutoyo , Mekhaiel David , Marini Arianna , Jore Matthijs M. , Søgaard Max M. , Jørgensen Thomas , de Jongh Willem A. , Sauerwein Robert W. , Long Carole A. , Biswas Sumi , Higgins Matthew K.
Published: September 2018

The quest to develop an effective malaria vaccine remains a major priority in the fight against global infectious disease. An approach with great potential is a transmission-blocking vaccine which induces antibodies that prevent establishment of a productive infection in mosquitos that feed on infected humans, thereby stopping the transmission cycle. One of the most promising targets for such a vaccine is the gamete surface protein, Pfs48/45. Here we establish a system for production of full-length Pfs48/45 and use this to raise a panel of monoclonal antibodies. We map the binding regions of these antibodies on Pfs48/45 and correlate the location of their epitopes with their transmission-blocking activity. Finally, we present the structure of the C-terminal domain of Pfs48/45 bound to the most potent transmission-blocking antibody, and provide key molecular information for future structure-guided immunogen design.
Rechargeable potassium-ion batteries with honeycomb-layered tellurates as high voltage cathodes and fast potassium-ion conductors
Authors: Masese Titus , Yoshii Kazuki , Yamaguchi Yoichi , Okumura Toyoki , Huang Zhen-Dong , Kato Minami , Kubota Keigo , Furutani Junya , Orikasa Yuki , Senoh Hiroshi , Sakaebe Hikari , Shikano Masahiro
Published: September 2018

Rechargeable potassium-ion batteries have been gaining traction as not only promising low-cost alternatives to lithium-ion technology, but also as high-voltage energy storage systems. However, their development and sustainability are plagued by the lack of suitable electrode materials capable of allowing the reversible insertion of the large potassium ions. Here, exploration of the database for potassium-based materials has led us to discover potassium ion conducting layered honeycomb frameworks. They show the capability of reversible insertion of potassium ions at high voltages (~4 V for K2Ni2TeO6) in stable ionic liquids based on potassium bis(trifluorosulfonyl) imide, and exhibit remarkable ionic conductivities e.g. ~0.01 mS cm−1 at 298 K and ~40 mS cm–1 at 573 K for K2Mg2TeO6. In addition to enlisting fast potassium ion conductors that can be utilised as solid electrolytes, these layered honeycomb frameworks deliver the highest voltages amongst layered cathodes, becoming prime candidates for the advancement of high-energy density potassium-ion batteries.
Exacerbated fires in Mediterranean Europe due to anthropogenic warming projected with non-stationary climate-fire models
Authors: Turco Marco , Rosa-Cánovas Juan José , Bedia Joaquín , Jerez Sonia , Montávez Juan Pedro , Llasat Maria Carmen , Provenzale Antonello
Published: September 2018

The observed trend towards warmer and drier conditions in southern Europe is projected to continue in the next decades, possibly leading to increased risk of large fires. However, an assessment of climate change impacts on fires at and above the 1.5 °C Paris target is still missing. Here, we estimate future summer burned area in Mediterranean Europe under 1.5, 2, and 3 °C global warming scenarios, accounting for possible modifications of climate-fire relationships under changed climatic conditions owing to productivity alterations. We found that such modifications could be beneficial, roughly halving the fire-intensifying signals. In any case, the burned area is robustly projected to increase. The higher the warming level is, the larger is the increase of burned area, ranging from ~40% to ~100% across the scenarios. Our results indicate that significant benefits would be obtained if warming were limited to well below 2 °C.
Frustrated endocytosis controls contractility-independent mechanotransduction at clathrin-coated structures
Authors: Baschieri Francesco , Dayot Stéphane , Elkhatib Nadia , Ly Nathalie , Capmany Anahi , Schauer Kristine , Betz Timo , Vignjevic Danijela Matic , Poincloux Renaud , Montagnac Guillaume
Published: September 2018

It is generally assumed that cells interrogate the mechanical properties of their environment by pushing and pulling on the extracellular matrix (ECM). For instance, acto-myosin-dependent contraction forces exerted at focal adhesions (FAs) allow the cell to actively probe substrate elasticity. Here, we report that a subset of long-lived and flat clathrin-coated structures (CCSs), also termed plaques, are contractility-independent mechanosensitive signaling platforms. We observed that plaques assemble in response to increasing substrate rigidity and that this is independent of FAs, actin and myosin-II activity. We show that plaque assembly depends on αvβ5 integrin, and is a consequence of frustrated endocytosis whereby αvβ5 tightly engaged with the stiff substrate locally stalls CCS dynamics. We also report that plaques serve as platforms for receptor-dependent signaling and are required for increased Erk activation and cell proliferation on stiff environments. We conclude that CCSs are mechanotransduction structures that sense substrate rigidity independently of cell contractility.
Microscopic origin of Cooper pairing in the iron-based superconductor Ba1−xKxFe2As2
Authors: Böhm Thomas , Kretzschmar Florian , Baum Andreas , Rehm Michael , Jost Daniel , Hosseinian Ahangharnejhad Ramez , Thomale Ronny , Platt Christian , Maier Thomas A. , Hanke Werner , Moritz Brian , Devereaux Thomas P. , Scalapino Douglas J. , Maiti Saurabh , Hirschfeld Peter J. , Adelmann Peter , Wolf Thomas , Wen Hai-Hu , Hackl Rudi
Published: September 2018

Resolving the microscopic pairing mechanism and its experimental identification in unconventional superconductors is among the most vexing problems of contemporary condensed matter physics. We show that Raman spectroscopy provides an avenue towards this aim by probing the structure of the pairing interaction at play in an unconventional superconductor. As we study the spectra of the prototypical Fe-based superconductor Ba1−xKxFe2As2 for 0.22 ≤ x ≤ 0.70 in all symmetry channels, Raman spectroscopy allows us to distill the leading s-wave state. In addition, the spectra collected in the B1g symmetry channel reveal the existence of two collective modes which are indicative of the presence of two competing, yet sub-dominant, pairing tendencies of $$d_{x^2 - y^2}$$

d

x

2

-

y

2

symmetry type. A comprehensive functional Renormalization Group and random-phase approximation study on this compound confirms the presence of the two sub-leading channels, and consistently matches the experimental doping dependence of the related modes. The consistency between the experimental observations and the theoretical modeling suggests that spin fluctuations play a significant role in superconducting pairing.
Effect on Local Structure and Phase Transition of Perovskite-Type [N(CH3)4]2Zn1-xCuxBr4 (x = 0, 0.5, 0.7, and 1) Crystals with the Various Doping of Cu2+ Ions
Authors: Lim Ae Ran
Published: September 2018

This study focused on how the local structures in pure [N(CH3)4]2ZnBr4 crystal are affected by the partial replacement of Zn2+ ions with Cu2+ ions. The structures and phase transition temperatures TC of perovskite-type [N(CH3)4]2Zn1-xCuxBr4 (x = 0, 0.5, 0.7, and 1) mixed crystals were almost unchanged by the partial doping of Cu2+ ions. The environments for the local structures of [N(CH3)4]2Zn1-xCuxBr4 mixed systems were studied according to differences in the chemical shifts of the 1H magic angle spinning (MAS) NMR, 13C cross-polarization (CP)/MAS NMR, and 14N NMR spectra. The 1H and 13C NMR results showed that the local environments of 1H and 13C nuclei near TC are not affected by substituting Zn2+ ions with Cu2+ ions, whereas the 14N NMR results showed that the local environment is affected near TC. Consequently, the main indicators of the phase transition in [N(CH3)4]2Zn1-xCuxBr4 are related to the ferroelastic characteristics with different orientations.
Trade-Off Analysis to Determine Environmental Flows in a Highly Regulated Watershed
Authors: Pang Aiping , Li Chunhui , Sun Tao , Yang Wei , Yang Zhifeng
Published: September 2018

In this study, we proposed an approach to recommend environmental flows in highly regulated areas, considering the multiple time scales of hydrological processes and water requirements. Water resources were seasonally allocated to the agricultural sector using a benefit-maximizing model, based on water deficiency at different crop growth stages. The economic feedback was evaluated after securing different levels of initial environmental flows. The final environmental flows were recommended to maintain a balance between the ecosystem and irrigation water needs. A case study was applied in the Baiyangdian watershed, China. The results show that a benefit-maximizing model can reduce the total economic losses to the maximum potential, which contributes to alleviating water use conflicts between agriculture and the ecosystem. However, the environmental flows cannot be maintained without the sacrifice of production losses, except for in extremely wet years. Average environmental flows could be secured at around 3.1, 4.3 and 5.4 × 108m3in dry, average, and wet years, respectively, with less than 10% production loss. Additional water transfer projects, as well as economic compensation strategies, are suggested to meet both ecosystem and agricultural needs. The planned economic compensation during 2010–2015 was 16.3 × 108Yuan, giving priority to securing environmental flows, and accounting for 7% of the total agricultural output value. The suggested amount of water resource transferred by the South-to-North Transfer Projects was 19 × 108m3, which is enough to alleviate water use conflicts between different stakeholders in dry years. This study provided a method to protect ecosystems in a more sustainable way.
Continuous positive airway pressure therapy for obstructive sleep apnoea and psychotropic drug use: a retrospective observational matched-cohort study
Authors: Delbarre Angélique , Gagnadoux Frédéric , Gohier Bénédicte , Pelletier-Fleury Nathalie
Published: September 2018

Patients with obstructive sleep apnoea (OSA) frequently present symptoms of depression, anxiety and insomnia and continuous positive airway pressure (CPAP) can improve these symptoms. Using a real-world administrative database, we analysed the trend of psychotropic drug use (antidepressants, anxiolytics and hypnotics) on a long-term period in OSA individuals before-after CPAP initiation. A total of 869 OSA individuals to whom psychotropic drugs were prescribed were followed for 4 years. They were matched to 2,607 non-OSA individuals, who were similar in terms of demographics, chronic diseases and care consumption. Generalized estimating equations models were used to compare psychotropic drug defined daily doses (DDD). Results showed no significant differences in mean trends of psychotropic drug DDD between OSA individuals and non-OSA matched controls during the three years following CPAP initiation. Only time had a significant effect on DDD, which decreased in both groups: −9% in Y1 and −17% in Y3, compared to Y0 (p-values < 0.0001). Hence, CPAP therapy does not result in an earlier decrease of psychotropic drug use in OSA individuals compared to non-OSA matched controls. Further studies are needed to analyse long-term psychotropic drug use, particularly in non-adherent OSA individuals.
Thermal management of epidermal electronic devices/skin system considering insensible sweating
Authors: Nie Shuang , Zhang Chenxi , Song Jizhou
Published: September 2018

Thermal management of the system consisting of epidermal electronics devices (EEDs) and skin is critically important since a few degrees in temperature increase may induce thermal discomfort. In this paper, considering insensible sweating, a three-dimensional analytical thermal model, validated by finite element analysis, is developed to derive analytical expressions for the steady temperature distributions in the EED/skin system. The influences of various parameters including the thickness and thermal conductivity of the substrate in EEDs on the maximum skin temperature are investigated. The comfort analysis is then carried out based on the model to provide design guidelines for optimizing the geometric and material properties of EEDs to avoid the adverse thermal effects. These results pave the theoretical foundation for thermal management of EEDs/skin system in practical applications.
Biosafety assessment of water samples from Wanzhou watershed of Yangtze Three Gorges Reservoir in the quiet season in Caenorhabditis elegans
Authors: Xiao Guosheng , Zhao Li , Huang Qian , Du Huihui , Guo Dongqin , Xia Mingxing , Li Guangman , Chen Zongxiang , Wang Dayong
Published: September 2018

We here employed a model animal of Caenorhabditis elegans to perform toxicity assessment of original surface water samples collected from Three Gorges Reservoir (TGR) in the quiet season in Wanzhou, Chongqing. Using some sublethal endpoints, including lifespan, body length, locomotion behavior, brood size, and intestinal reactive oxygen species (ROS) induction, we found that the examined five original surface water samples could not cause toxicity on wild-type nematodes. Nevertheless, the surface water sample collected from backwater area induced the significant increase in expressions of genes (sod-2 and sod-3) encoding Mn-SODs in wild-type nematodes. Among the examined five original surface water samples, exposure to the original surface water sample collected from backwater area could further cause the toxicity in decreasing locomotion behavior and in inducing intestinal ROS production in sod-3 mutant nematodes. Moreover, the solid phase of surface water sample collected from backwater area might mainly contribute to the observed toxicity in sod-3 mutant nematodes. Our results are helpful for understanding the potential effects of surface water in the TGR region in the quiet season on environmental organisms.
Anomalous behavior of membrane fluidity caused by copper-copper bond coupled phospholipids
Authors: Jiang Xiankai , Zhang Jinjin , Zhou Bo , Li Pei , Hu Xiaojuan , Zhu Zhi , Tan Yanwen , Chang Chao , Lü Junhong , Song Bo
Published: September 2018

Membrane fluidity, essential for cell functions, is obviously affected by copper, but the molecular mechanism is poorly understood. Here, we unexpectedly observed that a decrease in phospholipid (PL) bilayer fluidity caused by Cu2+ was more significant than those by Zn2+ and Ca2+, while a comparable reduction occurred in the last two ions. This finding disagrees with the placement in the periodic table of Cu just next to Zn and far from Ca. The physical nature was revealed to be an anomalous attraction between Cu+ cations, as well as the induced motif of two phospholipids coupled by Cu-Cu bond (PL-diCu-PL). Namely, upon Cu2+ ion binding to a negatively charged phosphate group of lipid, Cu2+ was reduced to Cu+. The attraction of the cations then caused one Cu+ ion simultaneously binding to two lipids and another Cu+, resulting in the formation of PL-diCu-PL structure. In contrast, this attraction cannot occur in the cases of Zn and Ca ions. Remarkably, besides lipids, the phosphate group also widely exists in other biological molecules, including DNA, RNA, ADP and ATP. Our findings thus provide a new view for understanding the biological functions of copper and the mechanism underlying copper-related diseases, as well as lipid assembly.
The effect of serum triglyceride concentration on the outcome of acute pancreatitis: systematic review and meta-analysis
Authors: Kiss Lóránd , Fűr Gabriella , Mátrai Péter , Hegyi Péter , Ivány Emese , Cazacu Irina Mihaela , Szabó Imre , Habon Tamás , Alizadeh Hussain , Gyöngyi Zoltán , Vigh Éva , Erőss Bálint , Erős Adrienn , Ottoffy Máté , Czakó László , Rakonczay Zoltán
Published: September 2018

Elevated serum triglyceride concentration (seTG, >1.7 mM or >150 mg/dL) or in other words hypertriglyceridemia (HTG) is common in the populations of developed countries. This condition is accompanied by an increased risk for various diseases, such as acute pancreatitis (AP). It has been proposed that HTG could also worsen the course of AP. Therefore, in this meta-analysis, we aimed to compare the effects of various seTGs on the severity, mortality, local and systemic complications of AP, and on intensive care unit admission. 16 eligible studies, including 11,965 patients were retrieved from PubMed and Embase. The results showed that HTG significantly elevated the odds ratio (OR = 1.72) for severe AP when compared to patients with normal seTG (<1.7 mM). Furthermore, a significantly higher occurrence of pancreatic necrosis, persistent organ failure and renal failure was observed in groups with HTG. The rates of complications and mortality for AP were significantly increased in patients with seTG >5.6 mM or >11.3 mM versus <5.6 mM or <11.3 mM, respectively. We conclude that the presence of HTG worsens the course and outcome of AP, but we found no significant difference in AP severity based on the extent of HTG.
Kinetics of the invasion and egress processes of Babesia divergens, observed by time-lapse video microscopy
Authors: Sevilla Elena , González Luis Miguel , Luque Daniel , Gray Jeremy , Montero Estrella
Published: September 2018

Based on confocal fluorescence and bright field video microscopy, we present detailed observations on the processes of invasion and egress of erythrocytes by the apicomplexan parasite Babesia divergens. Time-lapse images reveal numerous unexpected findings associated with the dynamics of B. divergens and its ability to manipulate the erythrocyte during both processes in its asexual cycle under in vitro conditions. Despite the speed at which these processes occur and the small size of the parasite, we capture infective merozoites moving vigorously and causing striking deformations in the erythrocyte’s plasma membrane during an active invasion. We also observed intraerythrocytic dynamic stages as paired pyriforms, double paired pyriforms, tetrads, unattached pyriform sister cells and multiple parasite stages resulting in the release of large numbers of merozoites over a short period. Of considerable interest is that time-lapse images reveal a novel mechanism of egress used by B. divergens to exit the human erythrocyte. The release occurs when B. divergens parasites establish contacts with the plasma membrane of the erythrocyte from within, before exiting the cell. Visualization and analysis of the images enabled us to obtain useful information and broaden our knowledge of complex and crucial events involved with parasitisation of human erythrocytes by B. divergens.
Recovering Motor Activation with Chronic Peripheral Nerve Computer Interface
Authors: Eggers Thomas E. , Dweiri Yazan M. , McCallum Grant A. , Durand Dominique M.
Published: September 2018

Interfaces with the peripheral nerve provide the ability to extract motor activation and restore sensation to amputee patients. The ability to chronically extract motor activations from the peripheral nervous system remains an unsolved problem. In this study, chronic recordings with the Flat Interface Nerve Electrode (FINE) are employed to recover the activation levels of innervated muscles. The FINEs were implanted on the sciatic nerves of canines, and neural recordings were obtained as the animal walked on a treadmill. During these trials, electromyograms (EMG) from the surrounding hamstring muscles were simultaneously recorded and the neural recordings are shown to be free of interference or crosstalk from these muscles. Using a novel Bayesian algorithm, the signals from individual fascicles were recovered and then compared to the corresponding target EMG of the lower limb. High correlation coefficients (0.84 ± 0.07 and 0.61 ± 0.12) between the extracted tibial fascicle/medial gastrocnemius and peroneal fascicle/tibialis anterior muscle were obtained. Analysis calculating the information transfer rate (ITR) from the muscle to the motor predictions yielded approximately 5 and 1 bit per second (bps) for the two sources. This method can predict motor signals from neural recordings and could be used to drive a prosthesis by interfacing with residual nerves.
Draining phenomenon in closed narrow tubes pierced at the top: an experimental and theoretical analysis
Authors: Kumar Amit , Ray Subhabrata , Das Gargi
Published: September 2018

The phenomenon of draining, although ubiquitous in nature, has received scant attention especially in the meso-scale. We observe that closed top tubes drain by the inception of an axisymmetric ‘Taylor finger’ while a minute pierce of the top closure results in an altogether different physics with air entry from the top pushing the liquid out. Again, a coupled mechanism comprising full bore followed by film draining is observed for “too small” a top pierce at “high enough” Eotvos number. Top pierce initiates draining in dimensions which would not drain otherwise and finger entry hastens the process of draining. The myriad of phenomena thus exhibited is depicted as phase diagrams in vertical and inclined conduits. A mechanistic model has been proposed to predict draining and the onset of finger entry in vertical tubes.
Stable isotope measurements show increases in corn water use efficiency under deficit irrigation
Authors: Wu Youjie , Du Taisheng , Yuan Yusen , Shukla Manoj K.
Published: September 2018

Deficit irrigation has usually improved crop water use efficiency (WUE), but there are still gaps in our understanding of the mechanisms. Four irrigation treatments were a conventional furrow irrigation (CFI), border irrigation (BI), alternate furrow irrigation (AFI), and an AFI(M/2) (the amount of irrigation was 50% of the AFI). The volume of irrigation water applied were nearly the same for CFI, BI, and AFI. The isotope (δ18O and δD) method was used to quantify corn root water uptake (RWU) during 2013–2014. Compared to CFI and BI, corn yield and WUE were 17.0-30.2% and 13.3-33.8% higher in AFI, respectively. No significant yield reduction were observed between AFI and AFI(M/2). Corn RWU was more from deeper soil with increasing growth stage for AFI(M/2), AFI, and CFI, but from shallower depth for BI. The depth for RWU varied in the order of AFI(M/2)  > AFI > CFI > BI. The maximum root density was in the depth of 40–80 cm at the growing stage in AFI, and 4–26% more water was extracted from the wetter and deeper root zones. The WUE increased under deficit irrigation, and stimulated the root growth with attendant decreases in water loss to deep percolation.
Evaluation of the roles of the cytosolic N-terminus and His-rich loop of ZNT proteins using ZNT2 and ZNT3 chimeric mutants
Authors: Fukue Kazuhisa , Itsumura Naoya , Tsuji Natsuko , Nishino Katsutoshi , Nagao Masaya , Narita Hiroshi , Kambe Taiho
Published: September 2018

The physiological roles of Zn transporter (ZNT) proteins are being increasingly recognized, and three dimensional structures of ZNT bacterial homologs have facilitated our understanding of their biochemical characteristics at the molecular level. However, the biological role of the unique structural features of vertebrate ZNTs, which are absent in their bacterial homologues, is not completely understood. These ZNT sequences include a cytosolic His-rich loop between transmembrane helices IV and V and the cytosolic N-terminus. This study investigated the contribution of these features to zinc transport by ZNT proteins. The importance of the His residues in the cytosolic His-rich loop was investigated using ZNT2 Ala substitution and deletion mutants. The presence of His residues was not essential for zinc transport, even though they possibly participate in modulation of zinc transport activity. Furthermore, we determined the role of the N-terminus by characterizing ZNT2 and ZNT3 domain-swapped and deletion mutants. Unexpectedly, the N-terminus was also not essential for zinc transport by ZNT2 and the domain-swapped ZNT2 mutant, in which the cytosolic His-rich loop was substituted with that of ZNT3. These results provide molecular insights into understanding the roles of the cytosolic parts of ZNT2, ZNT3, and probably other members of their subgroup.
Direct-fed microbial supplementation influences the bacteria community composition of the gastrointestinal tract of pre- and post-weaned calves
Authors: Fomenky Bridget E. , Do Duy N. , Talbot Guylaine , Chiquette Johanne , Bissonnette Nathalie , Chouinard Yvan P. , Lessard Martin , Ibeagha-Awemu Eveline M.
Published: September 2018

This study investigated the effect of supplementing the diet of calves with two direct fed microbials (DFMs) (Saccharomyces cerevisiae boulardii CNCM I-1079 (SCB) and Lactobacillus acidophilus BT1386 (LA)), and an antibiotic growth promoter (ATB). Thirty-two dairy calves were fed a control diet (CTL) supplemented with SCB or LA or ATB for 96 days. On day 33 (pre-weaning, n = 16) and day 96 (post-weaning, n = 16), digesta from the rumen, ileum, and colon, and mucosa from the ileum and colon were collected. The bacterial diversity and composition of the gastrointestinal tract (GIT) of pre- and post-weaned calves were characterized by sequencing the V3-V4 region of the bacterial 16S rRNA gene. The DFMs had significant impact on bacteria community structure with most changes associated with treatment occurring in the pre-weaning period and mostly in the ileum but less impact on bacteria diversity. Both SCB and LA significantly reduced the potential pathogenic bacteria genera, Streptococcus and Tyzzerella_4 (FDR ≤ 8.49E-06) and increased the beneficial bacteria, Fibrobacter (FDR ≤ 5.55E-04) compared to control. Other potential beneficial bacteria, including Rumminococcaceae UCG 005, Roseburia and Olsenella, were only increased (FDR ≤ 1.30E-02) by SCB treatment compared to control. Furthermore, the pathogenic bacterium, Peptoclostridium, was reduced (FDR = 1.58E-02) by SCB only while LA reduced (FDR = 1.74E-05) Ruminococcus_2. Functional prediction analysis suggested that both DFMs impacted (p < 0.05) pathways such as cell cycle, bile secretion, proteasome, cAMP signaling pathway, thyroid hormone synthesis pathway and dopaminergic synapse pathway. Compared to the DFMs, ATB had similar impact on bacterial diversity in all GIT sites but greater impact on the bacterial composition of the ileum. Overall, this study provides an insight on the bacteria genera impacted by DFMs and the potential mechanisms by which DFMs affect the GIT microbiota and may therefore facilitate development of DFMs as alternatives to ATB use in dairy calf management.
Cu-bearing stainless steel reduces cytotoxicity and crystals adhesion after ureteral epithelial cells exposing to calcium oxalate monohydrate
Authors: Cao Zhiqiang , Zhao Jing , Yang Ke
Published: September 2018

Calcium oxalate monohydrate (COM), which is the main component of encrustation, may result in cell membrane injury. In addition, cellular damage is suggested to be the primary event attributing to COM crystal binding. To study the interaction between cells and crystals after incubating with a Cu-bearing stainless steel (316L-Cu SS), MTS and flow cytometric analyses were used to assess the cellular responses. The results confirmed that 316L-Cu SS could inhibit cytotoxicity and cellular apoptosis of ureteral epithelial cells (UECs) after COM treatment. Furthermore, molecular expressions of Cu/Zn superoxide dismutase (CuZnSOD), which were evaluated by western blot analysis and real-time quantitative PCR (qPCR), indicated that 316L-Cu SS could inhibit the oxidative stress attributing to up-regulating of CuZnSOD. Moreover, the crystal adhesion cytokine CD44 was examined with western blot and qPCR, and the corresponding hyaluronic (HA) secreted into the medium was measured by enzyme-linked immunosorbent assay (ELISA). All results were confirmed that the expressions of cells cultured with 316L-Cu SS were down-regulated, demonstrating the inhibitory performance of 316L-Cu SS against crystal adhesion.
Metabolite accumulation and metabolic network in developing roots of Rehmannia glutinosa reveals its root developmental mechanism and quality
Authors: Zhou Yanqing , Yang Ke , Zhang Dandan , Duan Hongying , Liu Yongkang , Guo Mengmeng
Published: September 2018

Rehmannia glutinosa root contains many compounds with important medicinal properties and nutritional benefits, but only more than 140 compounds have been reported so far. Many other compounds and their accumulation and metabolic networks during its development remain unclear. In order to clarify them, its metabolic profiles at three different developmental stages were analyzed using untargeted LC-MS analysis. Multivariate analysis revealed that 434 metabolites differently accumulated in its different stages, suggesting different change trends. The metabolites having the same trend share common metabolic pathways, the metabolites showing increasing contents during its development have medical and nutritional values, and some mature root-specific metabolites may be better candidates for its quality control; 434 metabolites were mapped onto 111 KEGG pathways including 62 enzymes, whose increasing and decreasing patterns were shown during its development. Some metabolites complicatedly interacted with some enzymes and the top-10 pathways enriched from 111 KEGG pathways in network analysis. These findings extended the dataset of its identified compounds, and revealed that its development and quality were associated with the accumulation of different metabolites. Our work will lay the foundation for the better understanding of its chemical constituents, quality and developmental mechanism.
A quantitative analysis of 3D-cell distribution in regenerative muscle-skeletal system with synchrotron X-ray computed microtomography
Authors: Tesařová Markéta , Mancini Lucia , Simon Andras , Adameyko Igor , Kaucká Markéta , Elewa Ahmed , Lanzafame Gabriele , Zhang Yi , Kalasová Dominika , Szarowská Bára , Zikmund Tomáš , Novotná Marie , Kaiser Jozef
Published: September 2018

One of the greatest enigmas of modern biology is how the geometry of muscular and skeletal structures are created and how their development is controlled during growth and regeneration. Scaling and shaping of vertebrate muscles and skeletal elements has always been enigmatic and required an advanced technical level in order to analyse the cell distribution in 3D. In this work, synchrotron X-ray computed microtomography (µCT) and chemical contrasting has been exploited for a quantitative analysis of the 3D-cell distribution in tissues of a developing salamander (Pleurodeles waltl) limb – a key model organism for vertebrate regeneration studies. We mapped the limb muscles, their size and shape as well as the number and density of cells within the extracellular matrix of the developing cartilage. By using tomographic approach, we explored the polarity of the cells in 3D, in relation to the structure of developing joints. We found that the polarity of chondrocytes correlates with the planes in joint surfaces and also changes along the length of the cartilaginous elements. Our approach generates data for the precise computer simulations of muscle-skeletal regeneration using cell dynamics models, which is necessary for the understanding how anisotropic growth results in the precise shapes of skeletal structures.
Artificial Light at Night Affects Emergence from a Refuge and Space Use in Guppies
Authors: Kurvers R. H. J. M. , Drägestein J. , Hölker F. , Jechow A. , Krause J. , Bierbach D.
Published: September 2018

Artificial light at night (ALAN) is a major form of anthropogenic pollution. ALAN is well known to affect different behaviours during nighttime, when changes in light conditions often have immediate consequences for the trade-offs individuals experience. How ALAN affects daytime behaviours, however, has received far less attention. Here we studied how ALAN affected daytime personality traits and learning ability. We exposed Trinidadian guppies,Poecilia reticulata, for 10 weeks to different ALAN levels: bright light (24 hrs bright light, ~5,000 lx), dim light (12 hrs bright light; 12 hrs dim light, ~0.5 lx) and control (12 hrs bright light; 12 hrs dark). Afterwards, we tested how the treatments affected diurnal emergence from a refuge, space use, activity, sociability and the ability to memorize the location of companion fish. Individuals exposed to the light treatments (both dim and bright light) emerged quicker from a refuge and fish from the bright light treatment spent relatively more time in the open area of the arena. ALAN did not affect any of the other behaviours, although memory could not be tested since fish did not learn the companions’ location. Our results demonstrate that ALAN, next to affecting nocturnal behaviours, can also affect key diurnal behavioural processes, associated with risk-taking.
Modulation effects of the East Asian winter monsoon on El Niño-related rainfall anomalies in southeastern China
Authors: Ma Tianjiao , Chen Wen , Feng Juan , Wu Renguang
Published: September 2018

The present study investigates the modulation of the East Asian winter monsoon (EAWM) in the impacts of El Niño on the wintertime rainfall anomalies in southeastern China. Here, the variability of the EAWM that is independent of ENSO is considered, which is referred to as EAWMres with a strong EAWMres denoting anomalous northerly winds. Results demonstrate that strong (weak) EAWMres weakens (enhances) the positive rainfall anomalies in southeastern China induced by El Niño, because anomalous downward motion over the western North Pacific (WNP) associated with El Niño is weakened (strengthened) by strong (weak) EAWMres. The modulated convective activity over the WNP, on the one hand, changes the anomalous local Hadley circulation associated with El Niño. When El Niño is combined with strong (weak) EAWMres, anomalous local Hadley circulation is weak (strong) and the resultant anomalous upward motion is weak (strong) over southeastern China, leading to small (larger) positive rainfall anomalies there. On the other hand, the modulated WNP convective activity induces different low-level atmospheric responses to El Niño. During an El Niño winter with strong (weak) EAWMres, the weak (strong) anomalous suppressed convection produces a weak (strong) and insignificant (significant) anomalous low-level WNP anticyclone, resulting in correspondingly insignificant (significant) rainfall anomalies in southeastern China. Results from a linear baroclinic model further suggest that the different low-level atmospheric responses over WNP are mainly induced by different diabatic heating associated with El Niño under different EAWMres conditions.
The synergic effects of frailty on disability associated with urbanization, multimorbidity, and mental health: implications for public health and medical care
Authors: Lee Wei-Ju , Peng Li-Ning , Lin Chi-Hung , Lin Hui-Ping , Loh Ching-Hui , Chen Liang-Kung
Published: September 2018

Frailty is garnering increasing interest as a potential target in disability prevention. Since it is uncertain how frailty interacts with multimorbidity, urbanization, and mental health to affect disability, we investigated the epidemiology of frailty and its synergies with these factors. The study enrolled 20,898 participants aged 65 and older living in New Taipei city. All participants received face to face interview to assess frailty, multimorbidity, urban or rural residence, and mental health. Individual versus combined effects of risk factors were evaluated using the Rothman synergy index. Prevalence of frailty was 5.2% overall, 7.2% in multimorbid participants, 9.6% in rural residents, and 20.8% in those with mental disorders. Logistic regression, adjusted for age and sex, showed significant associations between disability and frailty (OR 8.5, 95% CI 6.4–11.2), multimorbidity (OR 1.3, 95% CI 1.0–1.6), urbanization (OR 1.3, 95% CI 1.0–1.7), and mental disorders (OR 7.3, 95% CI 5.6–9.5); these factors had a significant synergic effect on disability. Frailty is common in older adults and associated with disability, and was synergetic with multimorbidity, mental disorders, and residing rurally. Targeting frailty prevention and intervention needs a special attention on those vulnerable groups.
Optogenetic control of epithelial-mesenchymal transition in cancer cells
Authors: Zhou Xiaoxu , Wang Jian , Chen Junye , Qi Yuankai , Di Nan  , Jin Luhong , Qian Xiaohan , Wang Xinyi , Chen Qingyong , Liu Xu , Xu Yingke
Published: September 2018

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the initiation and promotion of cancer cell metastasis. The phosphoinositide 3-kinase (PI3K) signaling pathway has been demonstrated to be involved in TGF-β induced EMT, but the complicated TGF-β signaling network makes it challenging to dissect the important role of PI3K on regulation of EMT process. Here, we applied optogenetic controlled PI3K module (named ‘Opto-PI3K’), which based on CRY2 and the N-terminal of CIB1 (CIBN), to rapidly and reversibly control the endogenous PI3K activity in cancer cells with light. By precisely modulating the kinetics of PI3K activation, we found that E-cadherin is an important downstream target of PI3K signaling. Compared with TGF-β treatment, Opto-PI3K had more potent effect in down-regulation of E-cadherin expression, which was demonstrated to be regulated in a light dose-dependent manner. Surprisingly, sustained PI3K activation induced partial EMT state in A549 cells that is highly reversible. Furthermore, we demonstrated that Opto-PI3K only partially mimicked TGF-β effects on promotion of cell migration in vitro. These results reveal the importance of PI3K signaling in TGF-β induced EMT, suggesting other TGF-β regulated signaling pathways are necessary for the full and irreversible promotion of EMT in cancer cells. In addition, our study implicates the great promise of optogenetics in cancer research for mapping input-output relationships in oncogenic pathways.
The Value of Decreased Thyroid Hormone for Predicting Mortality in Adult Septic Patients: A Systematic Review and Meta-Analysis
Authors: Kim Jae Guk , Shin Hyungoo , Kim Wonhee , Lim Tae Ho , Jang Bohyoung , Cho Youngsuk , Choi Kyu-Sun , Ahn Chiwon , Lee Juncheol , Na Min Kyun
Published: September 2018

Decreased thyroid hormone (TH) has been considered as one of the potential predictors of mortality in sepsis. This study aimed to evaluate the prognostic impact of decreased TH on mortality in septic patients during intensive care unit (ICU) admission. We included studies that assessed thyroid function by measuring the serum thyroid hormone level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, commentaries, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 1,578 patients from eight studies were included. Triiodothyronine levels in non-survivors were relatively lower than that of survivors (6 studies; standardized mean difference [SMD] 2.31; 95% confidence interval (CI), 0.52–4.10; I2 = 97%; P = 0.01). Thyroxine levels in non-survivors were also lower than that of survivors (5 studies; SMD 2.40; 95% CI, 0.91–3.89). There were no statistically significant differences in thyroid-stimulating hormone levels between non-survivors and survivors. The present meta-analysis suggested that the decreased TH during ICU admission might be associated with the increase in mortality in adult septic patients. Hence, the measurement of TH could provide prognostic information on mortality in adult septic patients.
High-entropy alloy strengthened by in situ formation of entropy-stabilized nano-dispersoids
Authors: Gwalani Bharat , Pohan Rizaldy M. , Lee Junho , Lee Bin , Banerjee Rajarshi , Ryu Ho Jin , Hong Soon Hyung
Published: September 2018

A significant increase in compressive yield strength of the Al0.3CoCrFeMnNi high-entropy alloy (HEA) from 979 MPa to 1759 MPa was observed upon the introduction of 3 vol.% Y2O3. The HEAs were processed using spark plasma sintering of mechanically alloyed powders. Transmission electron microscopy and atom probe tomography confirmed the presence of compositionally complex nano-dispersoids in the Y2O3-added HEA. The significant increase in strength can be attributed to the nano-dispersoid strengthening coupled with grain refinement. Therefore, the in-situ formation of the compositionally complex nanoscale dispersoids during the alloy processing could be a novel approach to create entropy-stabilized oxide particles in strengthening of HEAs.
Multi-color lasing in chemically open droplet cavities
Authors: Zheng Lu , Zhi Min , Chan Yinthai , Khan Saif A.
Published: September 2018

In this paper, we demonstrate FRET-based multicolor lasing within chemically open droplet cavities that allow online modulation of the gain medium composition. To do this, we generated monodisperse microfluidic droplets loaded with coumarin 102 (donor), where the spherical droplets acted as whispering gallery mode (WGM) optical cavities in which coumarin 102 lasing (~ 470 nm) was observed. The lasing color was switched from blue to orange by the introduction of a second dye (acceptor, rhodamine 6 G) into the flowing droplet cavities; subsequent lasing from rhodamine 6 G (~ 590 nm) was observed together with the complete absence of coumarin 102 emission. The ability to control color switching online within the same droplet cavity enables sequential detection of multiple target molecules within or around the cavity. As a demonstration of this concept, we show how the presence of FITC-Dextran and methylene blue (MB) in the medium surrounding the lasing droplets can be sequentially detected by the blue and orange laser respectively. The method is simple and can be extended to a range of water-soluble dyes, thus enabling a wide spectral range for the lasing with the use of a single pump laser source.
Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape
Authors: Aliko Ardita , Kamińska Marta , Bergum Brith , Gawron Katarzyna , Benedyk Małgorzata , Lamont Richard J. , Malicki Stanisław , Delaleu Nicolas , Potempa Jan , Mydel Piotr
Published: September 2018

Peptidylarginine deiminase (PPAD) is a virulence factor unique to pathogenic Porphyromonas species, especially P. gingivalis. Mechanistically, PPAD activity, in conjunction with Arg-specific gingipains, generates protein fragments with citrullinated C-termini. Such polypeptides are potential de novo epitopes that are key drivers of rheumatoid arthritis. This process could underlie the observed clinical association between rheumatoid arthritis and periodontitis. However, the role of PPAD in host colonization by P. gingivalis and, subsequently, in triggering periodontitis is not known. Therefore, the aim of the current study was to delineate the role of PPAD in bacterial biofilm formation, and to define whether adherence to, invasion of, and host responses to bacteria of gingival keratinocytes depend on PPAD activity. We studied these aspects using PPAD-competent and PPAD-incompetent strains of P. gingivalis, and demonstrated that neither biofilm formation nor its composition was affected by PPAD activity. Similarly, flow cytometry revealed that PPAD did not impact the ability of P. gingivalis to adhere to and, subsequently, invade keratinocytes. Network analyses of gene expression patterns, however, revealed a group of host genes that were sensitive to PPAD activity (CXCL8, IL36G, CCL20, and IL1B). These genes can be categorized as potent immune modulators belonging to the interleukin 1 system, or chemoattractants of lymphocytes and neutrophils. Thus, we conclude that PPAD, although it is a potent modulator of the immune response, does not affect bacterial biofilm formation or the ability of P. gingivalis to adhere to and invade gingival epithelial cells.