bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating impedance-based growth-rate monitoring into a microfluidic cell culture platform for live-cell microscopy
Authors: Chawla Ketki , Bürgel Sebastian C. , Schmidt Gregor W. , Kaltenbach Hans-Michael , Rudolf Fabian , Frey Olivier , Hierlemann Andreas 
Published: May 2018

AbstractGrowth rate is a widely studied parameter for various cell-based biological studies. Growth rates of cell populations can be monitored in chemostats and micro-chemostats, where nutrients are continuously replenished. Here, we present an integrated microfluidic platform that enables long-term culturing of non-adherent cells as well as parallel and mutually independent continuous monitoring of (i) growth rates of cells by means of impedance measurements and of (ii) specific other cellular events by means of high-resolution optical or fluorescence microscopy. Yeast colonies were grown in a monolayer under culturing pads, which enabled high-resolution microscopy, as all cells were in the same focal plane. Upon cell growth and division, cells leaving the culturing area passed over a pair of electrodes and were counted through impedance measurements. The impedance data could then be used to directly determine the growth rates of the cells in the culturing area. The integration of multiple culturing chambers with sensing electrodes enabled multiplexed long-term monitoring of growth rates of different yeast strains in parallel. As a demonstration, we modulated the growth rates of engineered yeast strains using calcium. The results indicated that impedance measurements provide a label-free readout method to continuously monitor the changes in the growth rates of the cells without compromising high-resolution optical imaging of single cells.
Burkholderia bacteria use chemotaxis to find social amoeba Dictyostelium discoideum hosts
Authors: Shu Longfei , Zhang Bojie , Queller David C , Strassmann Joan E 
Published: May 2018

Abstract
A key question in cooperation is how to find the right partners and maintain cooperative relationships. This is especially challenging for horizontally transferred bacterial symbionts where relationships must be repeatedly established anew. In the social amoeba Dictyostelium discoideum farming symbiosis, two species of inedible Burkholderia bacteria (Burkholderia agricolaris and Burkholderia hayleyella) initiate stable associations with naive D. discoideum hosts and cause carriage of additional bacterial species. However, it is not clear how the association between D. discoideum and its carried Burkholderia is formed and maintained. Here, we look at precisely how Burkholderia finds its hosts. We found that both species of Burkholderia clones isolated from D. discoideum, but not other tested Burkholderia species, are attracted to D. discoideum supernatant, showing that the association is not simply the result of haphazard engulfment by the amoebas. The chemotactic responses are affected by both partners. We find evidence that B. hayleyella prefers D. discoideum clones that currently or previously carried Burkholderia, while B. agricolaris does not show this preference. However, we find no evidence of Burkholderia preference for their own host clone or for other hosts of their own species. We further investigate the chemical differences of D. discoideum supernatants that might explain the patterns shown above using a mass spectrometry based metabolomics approach. These results show that these bacterial symbionts are able to preferentially find and to some extent choose their unicellular partners. In addition, this study also suggests that bacteria can actively search for and target phagocytic cells, which may help us better understand how bacteria interact with immune systems.
Uncovering the hidden impacts of inequality on mental health: a global study
Authors: Yu Shoukai 
Published: May 2018

AbstractWomen are nearly twice as likely as men to suffer from mental illness. This gender disparity in depressive disorders may relate to social inequalities and living standards across nations. Currently, these disparities were not reflected at the level of health policies. This study utilized global data for depressive disorders and socioeconomic data from the United Nations’ World Bank databases and Global Burden of Disease database to demonstrate the correlation between social inequality and gender disparities in mental health. This study investigated the association among the ratio of female to male depressive disorder rates, gross domestic product, the GINI Index, and the gender inequality index for 122 countries. The research yielded some major findings. First, there exists a significant correlation between gender inequality and gender disparities in mental health. Second, the GINI index is significantly associated with male—but not female—depressive disorder rates. Third, gender disparities in depressive disorders are associated with a country’s wealth. These findings can help to inform society, policy-makers, and clinicians to improve the overall health level globally.
Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy
Authors: Madan Babita , McDonald Mitchell J. , Foxa Gabrielle E. , Diegel Cassandra R. , Williams Bart O. , Virshup David M. 
Published: May 2018

AbstractDysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine (PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159 (ETC-159) had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably, simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family, mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors. Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.
Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study
Authors: Chau Ian , Park Joon Oh , Ryoo Baek-Yeol , Yen Chia-Jui , Poon Ronnie , Pastorelli Davide , Blanc Jean-Frédéric , Kudo Masatoshi , Pfiffer Tulio , Hatano Etsuro , Chung Hyun Cheol , Kopeckova Katerina , Phelip Jean-Marc , Brandi Giovanni , Ohkawa Shinichi , Li Chung-Pin , Okusaka Takuji , Hsu Yanzhi , Abada Paolo B. , Zhu Andrew X. 
Published: May 2018

Abstract

Background
Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH.

Methods
Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed.

Results
Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001).

Conclusions
Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.
REGγ deficiency suppresses tumor progression via stabilizing CK1ε in renal cell carcinoma
Authors: Chen Shaojun , Wang Qingwei , Wang Longsheng , Chen Hui , Gao Xiao , Gong Dongkui , Ma Junjie , Kubra Syeda , Yao Xudong , Li Xiaotao , Li Lei , Zhai Wei , Zheng Junhua 
Published: May 2018

AbstractRenal cell carcinoma (RCC) is the most common malignant disease of kidney in adults. The proteasome activator REGγ was previously reported to promote the degradation of multiple important regulatory proteins and involved in the progression and development of numerous human cancers. Here, we first reported that REGγ was upregulated in RCC and its upregulation was correlated with a poor prognosis in RCC patients. REGγ depletion obviously suppressed RCC cells proliferation in vitro and in vivo. Notably, casein kinase 1ε (CK1ε) was identified as a novel target of REGγ and knockdown of CK1ε effectively abolished the effect of REGγ depletion on RCC cells growth. Importantly, we also observed that REGγ depletion activated Hippo signaling pathway via stabilizing CK1ε in RCC, indicating the cross-talk between REGγ/CK1ε axis and Hippo pathway during RCC development. In conclusion, our findings suggested that REGγ played a pivotal role in the development of RCC and maybe helpful to identify new therapeutic strategies in the treatment of RCC.
Gamma synuclein is a novel Twist1 target that promotes TGF-β-induced cancer cell migration and invasion
Authors: Shao Ting , Song Peiying , Hua Hui , Zhang Hongying , Sun Xiangmin , Kong Qingbin , Wang Jiao , Luo Ting , Jiang Yangfu 
Published: May 2018

AbstractTransforming growth factor β (TGF-β) is critical for embryonic development, adult tissue homeostasis, and tumor progression. TGF-β suppresses tumors at early stage, but promotes metastasis at later stage through oncogenes such as Twist1. Gamma-synuclein (SNCG) is overexpressed in a variety of invasive and metastatic cancer. Here, we show that TGF-β induces SNCG expression by Smad-Twist1 axis, thus promoting TGF-β- and Twist1-induced cancer cell migration and invasion. We identify multiple Twist1-binding sites (E-boxes) in SNCG promoter. Chromatin immunoprecipitation and luciferase assays confirm the binding of Twist1 to the E-boxes of SNCG promoter sequence (−129/−1026 bp). Importantly, the Twist1-binding site close to the transcription initiation site is critical for the upregulation of SNCG expression by TGF-β and Twist1. Mutations of Twist1 motif on the SNCG promoter constructs markedly reduces the promoter activity. We further show that TGF-β induces Twist1 expression through Smad thereby enhancing the binding of Twist1 to SNCG promoter, upregulating SNCG promoter activity and increasing SNCG expression. SNCG knockdown abrogates TGF-β- or Twist1-induced cancer cell migration and invasion. Finally, SNCG knockdown inhibits the promotion of cancer metastasis by Twist1. Together, our data demonstrate that SNCG is a novel target of TGF-β-Smad-Twist1 axis and a mediator of Twist1-induced cancer metastasis.
Distinct roles of XPF-ERCC1 and Rad1-Rad10-Saw1 in replication-coupled and uncoupled inter-strand crosslink repair
Authors: Seol Ja-Hwan , Holland Cory , Li Xiaolei , Kim Christopher , Li Fuyang , Medina-Rivera Melisa , Eichmiller Robin , Gallardo Ignacio F. , Finkelstein Ilya J. , Hasty Paul , Shim Eun Yong , Surtees Jennifer A. , Lee Sang Eun 
Published: May 2018

AbstractYeast Rad1–Rad10 (XPF–ERCC1 in mammals) incises UV, oxidation, and cross-linking agent-induced DNA lesions, and contributes to multiple DNA repair pathways. To determine how Rad1–Rad10 catalyzes inter-strand crosslink repair (ICLR), we examined sensitivity to ICLs from yeast deleted forSAW1andSLX4, which encode proteins that interact physically with Rad1–Rad10 and bind stalled replication forks. Saw1, Slx1, and Slx4 are critical for replication-coupled ICLR inmus81deficient cells. Two rad1 mutations that disrupt interactions between Rpa1 and Rad1–Rad10 selectively disable non-nucleotide excision repair (NER) function, but retain UV lesion repair. Mutations in the analogous region of XPF also compromised XPF interactions with Rpa1 and Slx4, and are proficient in NER but deficient in ICLR and direct repeat recombination. We propose that Rad1–Rad10 makes distinct contributions to ICLR depending on cell cycle phase: in G1, Rad1–Rad10 removes ICL via NER, whereas in S/G2, Rad1–Rad10 facilitates NER-independent replication-coupled ICLR.
Extremely stable graphene electrodes doped with macromolecular acid
Authors: Kwon Sung-Joo , Han Tae-Hee , Ko Taeg Yeoung , Li Nannan , Kim Youngsoo , Kim Dong Jin , Bae Sang-Hoon , Yang Yang , Hong Byung Hee , Kim Kwang S. , Ryu Sunmin , Lee Tae-Woo 
Published: May 2018

AbstractAlthough conventional p-type doping using small molecules on graphene decreases its sheet resistance (Rsh), it increases after exposure to ambient conditions, and this problem has been considered as the biggest impediment to practical application of graphene electrodes. Here, we report an extremely stable graphene electrode doped with macromolecular acid (perfluorinated polymeric sulfonic acid (PFSA)) as a p-type dopant. The PFSA doping on graphene provides not only ultra-high ambient stability for a very long time (> 64 days) but also high chemical/thermal stability, which have been unattainable by doping with conventional small-molecules. PFSA doping also greatly increases the surface potential (~0.8 eV) of graphene, and reduces its Rsh by ~56%, which is very important for practical applications. High-efficiency phosphorescent organic light-emitting diodes are fabricated with the PFSA-doped graphene anode (~98.5 cd A−1 without out-coupling structures). This work lays a solid platform for practical application of thermally-/chemically-/air-stable graphene electrodes in various optoelectronic devices.
Protein polarization driven by nucleoid exclusion of DnaK(HSP70)–substrate complexes
Authors: Collet Clémence , Thomassin Jenny-Lee , Francetic Olivera , Genevaux Pierre , Tran Van Nhieu Guy 
Published: May 2018

AbstractMany bacterial proteins require specific subcellular localization for function. How Escherichia coli proteins localize at one pole, however, is still not understood. Here, we show that the DnaK (HSP70) chaperone controls unipolar localization of the Shigella IpaC type III secretion substrate. While preventing the formation of lethal IpaC aggregates, DnaK promoted the incorporation of IpaC into large and dynamic complexes (LDCs) restricted at the bacterial pole through nucleoid occlusion. Unlike stable polymers and aggregates, LDCs show dynamic behavior indicating that nucleoid occlusion also applies to complexes formed through transient interactions. Fluorescence recovery after photobleaching analysis shows DnaK-IpaC exchanges between opposite poles and DnaKJE-mediated incorporation of immature substrates in LDCs. These findings reveal a key role for LDCs as reservoirs of functional DnaK-substrates that can be rapidly mobilized for secretion triggered upon bacterial contact with host cells.
Tuning the interplay between nematicity and spin fluctuations in Na1−xLi
x
FeAs superconductors
Authors: Baek S.-H. , Bhoi Dilip , Nam Woohyun , Lee Bumsung , Efremov D. V. , Büchner B. , Kim Kee Hoon 
Published: May 2018

AbstractStrong interplay of spin and charge/orbital degrees of freedom is the fundamental characteristic of the iron-based superconductors (FeSCs), which leads to the emergence of a nematic state as a rule in the vicinity of the antiferromagnetic state. Despite intense debate for many years, however, whether nematicity is driven by spin or orbital fluctuations remains unsettled. Here, by use of transport, magnetization, and 75As nuclear magnetic resonance (NMR) measurements, we show a striking transformation of the relationship between nematicity and spin fluctuations (SFs) in Na1−xLi
x
FeAs; For x ≤ 0.02, the nematic transition promotes SFs. In contrast, for x ≥ 0.03, the system undergoes a non-magnetic phase transition at a temperature T0 into a distinct nematic state that suppresses SFs. Such a drastic change of the spin fluctuation spectrum associated with nematicity by small doping is highly unusual, and provides insights into the origin and nature of nematicity in FeSCs.
Introduced species that overcome life history tradeoffs can cause native extinctions
Authors: Catford Jane A. , Bode Michael , Tilman David 
Published: May 2018

AbstractIntroduced species threaten native biodiversity, but whether exotic species can competitively displace native species remains contested. Building on theory that predicts multi-species coexistence based on a competition-colonisation tradeoff, we derive a mechanistic basis by which human-mediated species invasions could cause extinctions through competitive displacement. In contrast to past invasions, humans principally introduce modern invaders, repeatedly and in large quantities, and in ways that can facilitate release from enemies and competitors. Associated increases in exotic species’ propagule rain, survival and competitive ability could enable some introduced species to overcome the tradeoffs that constrain all other species. Using evidence from metacommunity models, we show how species introductions could disrupt species coexistence, generating extinction debts, especially when combined with other forms of anthropogenic environmental change. Even though competing species have typically coexisted following past biogeographic migrations, the multiplicity and interactive impacts of today’s threats could change some exotic species into agents of extinction.
Distinct epigenomic patterns are associated with haploinsufficiency and predict risk genes of developmental disorders
Authors: Han Xinwei , Chen Siying , Flynn Elise , Wu Shuang , Wintner Dana , Shen Yufeng 
Published: May 2018

AbstractHaploinsufficiency is a major mechanism of genetic risk in developmental disorders. Accurate prediction of haploinsufficient genes is essential for prioritizing and interpreting deleterious variants in genetic studies. Current methods based on mutation intolerance in population data suffer from inadequate power for genes with short transcripts. Here we show haploinsufficiency is strongly associated with epigenomic patterns, and develop a computational method (Episcore) to predict haploinsufficiency leveraging epigenomic data from a broad range of tissue and cell types by machine learning methods. Based on data from recent exome sequencing studies on developmental disorders, Episcore achieves better performance in prioritizing likely-gene-disrupting (LGD) de novo variants than current methods. We further show that Episcore is less-biased by gene size, and complementary to mutation intolerance metrics for prioritizing LGD variants. Our approach enables new applications of epigenomic data and facilitates discovery and interpretation of novel risk variants implicated in developmental disorders.
Author Correction: Oxidative rearrangement of (+)-sesamin by CYP92B14 co-generates twin dietary lignans in sesame
Authors: Murata Jun , Ono Eiichiro , Yoroizuka Seigo , Toyonaga Hiromi , Shiraishi Akira , Mori Shoko , Tera Masayuki , Azuma Toshiaki , Nagano Atsushi J. , Nakayasu Masaru , Mizutani Masaharu , Wakasugi Tatsuya , Yamamoto Masayuki P. , Horikawa Manabu 
Published: May 2018

The original version of of the Supplementary Information associated with this Article inadvertently omitted oligonucleotide primer sequences from Supplementary Table 3 and Supplementary Methods describing the molecular cloning of CYP92B14, CPR1 and CYP81Q cDNA fragments. The HTML has been updated to include a corrected version of the Supplementary Information.
The Relationship between Robot’s Nonverbal Behaviour and Human’s Likability Based on Human’s Personality
Authors: Thepsoonthorn Chidchanok , Ogawa Ken-ichiro , Miyake Yoshihiro 
Published: May 2018

AbstractAt current state, although robotics technology has been immensely developed, the uncertainty to completely engage in human-robot interaction is still growing among people. Many current studies then started to concern about human factors that might influence human’s likability like human’s personality, and found that compatibility between human’s and robot’s personality (expressions of personality characteristics) can enhance human’s likability. However, it is still unclear whether specific means and strategy of robot’s nonverbal behaviours enhances likability from human with different personality traits and whether there is a relationship between robot’s nonverbal behaviours and human’s likability based on human’s personality. In this study, we investigated and focused on the interaction via gaze and head nodding behaviours (mutual gaze convergence and head nodding synchrony) between introvert/extravert participants and robot in two communication strategies (Backchanneling and Turn-taking). Our findings reveal that the introvert participants are positively affected by backchanneling in robot’s head nodding behaviour, which results in substantial head nodding synchrony whereas the extravert participants are positively influenced by turn-taking in gaze behaviour, which leads to significant mutual gaze convergence. This study demonstrates that there is a relationship between robot’s nonverbal behaviour and human’s likability based on human’s personality.
Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages
Authors: Baltazar Ludmila Matos , Zamith-Miranda Daniel , Burnet Meagan C. , Choi Hyungwon , Nimrichter Leonardo , Nakayasu Ernesto S. , Nosanchuk Joshua D. 
Published: May 2018

AbstractDiverse pathogenic fungi secrete extracellular vesicles (EV) that contain macromolecules, including virulence factors that can modulate the host immune response. We recently demonstrated that the binding of monoclonal antibodies (mAb) modulates howHistoplasma capsulatumload and releases its extracellular vesicles (EV). In the present paper, we addressed a concentration-dependent impact on the fungus’ EV loading and release with different mAb, as well as the pathophysiological role of these EV during the host-pathogen interaction. We found that the mAbs differentially regulate EV content in concentration-dependent and independent manners. Enzymatic assays demonstrated that laccase activity in EV fromH.capsulatumopsonized with 6B7 was reduced, but urease activity was not altered. The uptake ofH.capsulatumby macrophages pre-treated with EV, presented an antibody concentration-dependent phenotype. The intracellular killing of yeast cells was potently inhibited in macrophages pre-treated with EV from 7B6 (non-protective) mAb-opsonizedH.capsulatumand this inhibition was associated with a decrease in the reactive-oxygen species generated by these macrophages. In summary, our findings show that opsonization quantitatively and qualitatively modifiesH.capsulatumEV load and secretion leading to distinct effects on the host’s immune effector mechanisms, supporting the hypothesis that EV sorting and secretion are dynamic mechanisms for a fine-tuned response by fungal cells.