bluuebunny/crossref_metadata_2025 huggingface dataset:
From the Colonial to Feminist IR: Feminist IR Studies, the Wider FSS/GPE Research Agenda, and the Questions of Value, Valuation, Security, and Violence
Authors: Agathangelou Anna M.
Published: November 2017

International relations (IR) feminists have significantly impacted the way we analyze the world and power. However, as Cynthia Enloe points out, “there are now signs—worrisome signs—that feminist analysts of international politics might be forgetting what they have shared” and are “making bricks to construct new intellectual barriers. That is not progress” (2015, 436). I agree. The project/process that has led to the separation/specialization of feminist security studies (FSS) and feminist global political economy (FGPE) does not constitute progress but instead ends up embodying forms of violence that erase the materialist bases of our intellectual labor's divisions (Agathangelou 1997), the historical and social constitution of our formations as intellectuals and subjects. This amnesiac approach evades our personal lives and colludes with those forces that allow for the violence that comes with abstraction. These “worrisome signs” should be explained if we are to move FSS and FGPE beyond a “merger” (Allison 2015) that speaks only to some issues and some humans in the global theater.
Sicheres Sprechen und Schlucken bei tracheotomierten, beatmeten Patientinnen und Patienten auf der Intensivstation
Authors: Fröhlich Martin R. , Boksberger Heidi , Barfuss-Schneider Claudia , Liem Esther , Petry Heidi
Published: November 2017

Zusammenfassung. Hintergrund: Auf der Intensivstation leiden 4 – 45 % der Patientinnen und Patienten unter anhaltender Ventilatorabhängigkeit und können aufgrund erschwerter Entwöhnung nicht verbal kommunizieren. Die Trachealkanüle beeinträchtigt unter anderem physiologische Prozesse beim Atmen und Schlucken. Das Passy Muir Sprechventil (PMV) ermöglicht Patientinnen und Patienten, am Beatmungsgerät zu sprechen und zu schlucken. Die Desensibilisierung des Larynx und Pharynx sowie ein unzureichender Schluckreflex lassen sich verhindern. Ziel und Methode: Im Rahmen eines multiprofessionellen Praxis- und Qualitätsentwicklungsprojekts mit theoretischen Schulungen und Praxisbegleitung implementierten wir das PMV, um tracheotomierten, beatmeten Patientinnen und Patienten sicheres Sprechen und Schlucken zu ermöglichen. Ergebnisse: Intensivpflegefachpersonen, Physiotherapeutinnen und Physiotherapeuten sowie Ärztinnen und Ärzte schätzten die Patientensicherheit durch den Einsatz des PMV als hoch ein. Bei neun Patientinnen und Patienten mit insgesamt 51 PMV-Anwendungen traten drei unerwünschte Ereignisse in Form von Atemnot und Sauerstoffsättigungsabfall ein. Ein Ereignis führte zum Abbruch der PMV-Anwendung. Schlussfolgerung: Durch die Kombination aus verbindlicher Schulung für das gesamte Behandlungsteam, Betreuung der Patientinnen und Patienten durch zwei Fachpersonen unterschiedlicher Berufsgruppen während des PMV-Einsatzes und einem neu erstellten handlungsleitenden Dokument liess sich ein hoher Grad an Patientensicherheit erreichen. Beatmete Patientinnen und Patienten auf der Intensivstation können sich mithilfe des PMV verbal mitteilen und besser schlucken. Komplikationen sind früh erkennbar und lassen sich wirksam beheben.
Graphene-edge dielectrophoretic tweezers for trapping of biomolecules
Authors: Barik Avijit , Zhang Yao , Grassi Roberto , Nadappuram Binoy Paulose , Edel Joshua B. , Low Tony , Koester Steven J. , Oh Sang-Hyun
Published: November 2017

The many unique properties of graphene, such as the tunable optical, electrical, and plasmonic response make it ideally suited for applications such as biosensing. As with other surface-based biosensors, however, the performance is limited by the diffusive transport of target molecules to the surface. Here we show that atomically sharp edges of monolayer graphene can generate singular electrical field gradients for trapping biomolecules via dielectrophoresis. Graphene-edge dielectrophoresis pushes the physical limit of gradient-force-based trapping by creating atomically sharp tweezers. We have fabricated locally backgated devices with an 8-nm-thick HfO2dielectric layer and chemical-vapor-deposited graphene to generate 10× higher gradient forces as compared to metal electrodes. We further demonstrate near-100% position-controlled particle trapping at voltages as low as 0.45 V with nanodiamonds, nanobeads, and DNA from bulk solution within seconds. This trapping scheme can be seamlessly integrated with sensors utilizing graphene as well as other two-dimensional materials.
O-GlcNAcylation is required for B cell homeostasis and antibody responses
Authors: Wu Jung-Lin , Chiang Ming-Feng , Hsu Pan-Hung , Tsai Dong-Yen , Hung Kuo-Hsuan , Wang Ying-Hsiu , Angata Takashi , Lin Kuo-I
Published: November 2017

O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. Together, these results demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis, transduce BCR-mediated activation signals and activate humoral immunity.
Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1
Authors: Fujita Kyota , Mao Ying , Uchida Shigenori , Chen Xigui , Shiwaku Hiroki , Tamura Takuya , Ito Hikaru , Watase Kei , Homma Hidenori , Tagawa Kazuhiko , Sudol Marius , Okazawa Hitoshi
Published: November 2017

YAP and its neuronal isoform YAPdeltaC are implicated in various cellular functions. We found that expression of YAPdeltaC during development, but not adulthood, rescued neurodegeneration phenotypes of mutant ataxin-1 knock-in (Atxn1-KI) mice. YAP/YAPdeltaC interacted with RORα via the second WW domain and served as co-activators of its transcriptional activity. YAP/YAPdeltaC formed a transcriptional complex with RORα on cis-elements of target genes and regulated their expression. Both normal and mutant Atxn1 interacted with YAP/YAPdeltaC, but only mutant Atxn1 depleted YAP/YAPdeltaC from the RORα complex to suppress transcription on short timescales. Over longer periods, mutant Atxn1 also decreased RORα in vivo. Genetic supplementation of YAPdeltaC restored the RORα and YAP/YAPdeltaC levels, recovered YAP/YAPdeltaC in the RORα complex and normalized target gene transcription in Atxn1-KI mice in vivo. Collectively, our data suggest that functional impairment of YAP/YAPdeltaC by mutant Atxn1 during development determines the adult pathology of SCA1 by suppressing RORα-mediated transcription.
In vivo transplantation of 3D encapsulated ovarian constructs in rats corrects abnormalities of ovarian failure
Authors: Sittadjody Sivanandane , Saul Justin M. , McQuilling John P. , Joo Sunyoung , Register Thomas C. , Yoo James J. , Atala Anthony , Opara Emmanuel C.
Published: November 2017

Safe clinical hormone replacement (HR) will likely become increasingly important in the growing populations of aged women and cancer patients undergoing treatments that ablate the ovaries. Cell-based HRT (cHRT) is an alternative approach that may allow certain physiological outcomes to be achieved with lower circulating hormone levels than pharmacological means due to participation of cells in the hypothalamus-pituitary-ovary feedback control loop. Here we describe the in vivo performance of 3D bioengineered ovarian constructs that recapitulate native cell–cell interactions between ovarian granulosa and theca cells as an approach to cHRT. The constructs are fabricated using either Ca++ or Sr++ to crosslink alginate. Following implantation in ovariectomized (ovx) rats, the Sr++-cross-linked constructs achieve stable secretion of hormones during 90 days of study. Further, we show these constructs with isogeneic cells to be effective in ameliorating adverse effects of hormone deficiency, including bone health, uterine health, and body composition in this rat model.
Inference of differentiation time for single cell transcriptomes using cell population reference data
Authors: Sun Na , Yu Xiaoming , Li Fang , Liu Denghui , Suo Shengbao , Chen Weiyang , Chen Shirui , Song Lu , Green Christopher D. , McDermott Joseph , Shen Qin , Jing Naihe , Han Jing-Dong J.
Published: November 2017

Single-cell RNA sequencing (scRNA-seq) is a powerful method for dissecting intercellular heterogeneity during development. Conventional trajectory analysis provides only a pseudotime of development, and often discards cell-cycle events as confounding factors. Here using matched cell population RNA-seq (cpRNA-seq) as a reference, we developed an “iCpSc” package for integrative analysis of cpRNA-seq and scRNA-seq data. By generating a computational model for reference “biological differentiation time” using cell population data and applying it to single-cell data, we unbiasedly associated cell-cycle checkpoints to the internal molecular timer of single cells. Through inferring a network flow from cpRNA-seq to scRNA-seq data, we predicted a role of M phase in controlling the speed of neural differentiation of mouse embryonic stem cells, and validated it through gene knockout (KO) experiments. By linking temporally matched cpRNA-seq and scRNA-seq data, our approach provides an effective and unbiased approach for identifying developmental trajectory and timing-related regulatory events.
Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance
Authors: Martin Lesley-Ann , Ribas Ricardo , Simigdala Nikiana , Schuster Eugene , Pancholi Sunil , Tenev Tencho , Gellert Pascal , Buluwela Laki , Harrod Alison , Thornhill Allan , Nikitorowicz-Buniak Joanna , Bhamra Amandeep , Turgeon Marc-Olivier , Poulogiannis George , Gao Qiong , Martins Vera , Hills Margaret , Garcia-Murillas Isaac , Fribbens Charlotte , Patani Neill , Li Zheqi , Sikora Matthew J. , Turner Nicholas , Zwart Wilbert , Oesterreich Steffi , Carroll Jason , Ali Simak , Dowsett Mitch
Published: November 2017

Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1
Y537C
and ESR1
Y537S
mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.
Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis
Authors: Han Hye-Sook , Choi Byeong Hun , Kim Jun Seok , Kang Geon , Koo Seung-Hoi
Published: November 2017

Liver plays a crucial role in controlling energy homeostasis in mammals, although the exact mechanism by which it influences other peripheral tissues has yet to be addressed. Here we show that Creb regulates transcriptional co-activator (Crtc) 2 is a major regulator of whole-body energy metabolism. Crtc2 liver-specific knockout lowers blood glucose levels with improved glucose and insulin tolerance. Liver-specific knockout mice display increased energy expenditure with smaller lipid droplets in adipose depots. Both plasma and hepatic Fgf21 levels are increased in Crtc2 liver-specific knockout mice, as a result of the reduced miR-34a expression regulated by Creb/Crtc2 and the induction of Sirt1 and Pparα. Ectopic expression of miR-34a reverses the metabolic changes in knockout liver. We suggest that Creb/Crtc2 negatively regulates the Sirt1/Pparα/Fgf21 axis via the induction of miR-34a under diet-induced obesity and insulin-resistant conditions.
Inhibiting Rho kinase promotes goal-directed decision making and blocks habitual responding for cocaine
Authors: Swanson Andrew M. , DePoy Lauren M. , Gourley Shannon L.
Published: November 2017

The prelimbic prefrontal cortex is necessary for associating actions with their consequences, enabling goal-directed decision making. We find that the strength of action–outcome conditioning correlates with dendritic spine density in prelimbic cortex, suggesting that new action–outcome learning involves dendritic spine plasticity. To test this, we inhibited the cytoskeletal regulatory factor Rho kinase. We find that the inhibitor fasudil enhances action–outcome memory, resulting in goal-directed behavior in mice that would otherwise express stimulus-response habits. Fasudil transiently reduces prelimbic cortical dendritic spine densities during a period of presumed memory consolidation, but only when paired with new learning. Fasudil also blocks habitual responding for cocaine, an effect that persists over time, across multiple contexts, and depends on actin polymerization. We suggest that Rho kinase inhibition promotes goal-oriented action selection by augmenting the plasticity of prelimbic cortical dendritic spines during the formation of new action–outcome memories.
BEX1 is an RNA-dependent mediator of cardiomyopathy
Authors: Accornero Federica , Schips Tobias G. , Petrosino Jennifer M. , Gu Shan-Qing , Kanisicak Onur , van Berlo Jop H. , Molkentin Jeffery D.
Published: November 2017

Regulation of mRNA splicing, processing and stability is increasingly recognized as a critical control point in dynamically altering gene expression during stress or disease. Very little is understood of this process in heart failure. Here, we show that BEX1 is a heart failure-induced gene functioning as an mRNA-associated protein that enhances expression of a subset of cardiac disease-promoting genes. Modeling the increase in BEX1 that occurs in disease, cardiac-specific BEX1 transgenic mice show worse cardiac disease with stress stimulation, whereas Bex1 gene-deleted mice are protected from heart failure-promoting insults. Proteomic and interactive screening assays show that BEX1 is part of a large ribonucleoprotein processing complex involved in regulating proinflammatory mRNA expression in the heart. Specifically, induction of BEX1 augments the stability and expression of AU-rich element containing mRNAs typically found within proinflammatory genes. Thus, BEX1 functions as an mRNA-dependent effector that augments pathology-promoting gene expression during heart failure.
Contributions of Zea mays subspecies mexicana haplotypes to modern maize
Authors: Yang Ning , Xu Xi-Wen , Wang Rui-Ru , Peng Wen-Lei , Cai Lichun , Song Jia-Ming , Li Wenqiang , Luo Xin , Niu Luyao , Wang Yuebin , Jin Min , Chen Lu , Luo Jingyun , Deng Min , Wang Long , Pan Qingchun , Liu Feng , Jackson David , Yang Xiaohong , Chen Ling-Ling , Yan Jianbing
Published: November 2017

Maize was domesticated from lowland teosinte (Zea mays ssp. parviglumis), but the contribution of highland teosinte (Zea mays ssp. mexicana, hereafter mexicana) to modern maize is not clear. Here, two genomes for Mo17 (a modern maize inbred) and mexicana are assembled using a meta-assembly strategy after sequencing of 10 lines derived from a maize-teosinte cross. Comparative analyses reveal a high level of diversity between Mo17, B73, and mexicana, including three Mb-size structural rearrangements. The maize spontaneous mutation rate is estimated to be 2.17 × 10−8 ~3.87 × 10−8 per site per generation with a nonrandom distribution across the genome. A higher deleterious mutation rate is observed in the pericentromeric regions, and might be caused by differences in recombination frequency. Over 10% of the maize genome shows evidence of introgression from the mexicana genome, suggesting that mexicana contributed to maize adaptation and improvement. Our data offer a rich resource for constructing the pan-genome of Zea mays and genetic improvement of modern maize varieties.
The gibberellin GID1-DELLA signalling module exists in evolutionarily ancient conifers
Authors: Du Ran , Niu Shihui , Liu Yang , Sun Xinrui , Porth Ilga , El-Kassaby Yousry A. , Li Wei
Published: November 2017

Gibberellins (GAs) participate in controlling various aspects of basic plant growth responses. With the exception of bryophytes, GA signalling in land plants, such as lycophytes, ferns and angiosperms, is mediated via GIBBERELLIN-INSENSITIVE DWARF1 (GID1) and DELLA proteins. To explore whether this GID1-DELLA mechanism is present in pines, we cloned an orthologue (PtGID1) of Arabidopsis AtGID1a and two putative DELLA proteins (PtDPL; PtRGA) from Pinus tabuliformis, a widespread indigenous conifer species in China, and studied their recombinant proteins. PtGID1 shares with AtGID1a the conserved HSL motifs for GA binding and an N-terminal feature that are essential for interaction with DELLA proteins. Indeed, A. thaliana 35S:PtGID1 overexpressors showed a strong GA-hypersensitive phenotype compared to the wild type. Interactions between PtGID1 and PtDELLAs, but also interactions between the conifer-angiosperm counterparts (i.e. between AtGID1 and PtDELLAs and between PtGID1 and AtDELLA), were detected in vivo. This demonstrates that pine has functional GID1-DELLA components. The Δ17-domains within PtDPL and PtRGA were identified as potential interaction sites within PtDELLAs. Our results show that PtGID1 has the ability to interact with DELLA and functions as a GA receptor. Thus, a GA-GID1-DELLA signalling module also operates in evolutionarily ancient conifers.
Mechanism in External Field-mediated Trapping of Bacteria Sensitive to Nanoscale Surface Chemical Structure
Authors: Tokonami Shiho , Shimizu Emi , Tamura Mamoru , Iida Takuya
Published: November 2017

Molecular imprinting technique enables the selective binding of nanoscale target molecules to a polymer film, within which their chemical structure is transcribed. Here, we report the successful production of mixed bacterial imprinted film (BIF) from several food poisoning bacteria by the simultaneous imprinting of their nanoscale surface chemical structures (SCS), and provide highly selective trapping of original micron-scale bacteria used in the production process of mixed BIF even for multiple kinds of bacteria in real samples. Particularly, we reveal the rapid specific identification of E. coli group serotypes (O157:H7 and O26:H11) using an alternating electric field and a quartz crystal microbalance. Furthermore, we have performed the detailed physicochemical analysis of the specific binding of SCS and molecular recognition sites (MRS) based on the dynamic Monte Carlo method under taking into account the electromagnetic interaction. The dielectrophoretic selective trapping greatly depends on change in SCS of bacteria damaged by thermal treatment, ultraviolet irradiation, or antibiotic drugs, which can be well explained by the simulation results. Our results open the avenue for an innovative means of specific and rapid detection of unknown bacteria for food safety and medicine from a nanoscale viewpoint.
Estrogen attenuates AGTR1 expression to reduce pancreatic β-cell death from high glucose
Authors: Kooptiwut Suwattanee , Wanchai Keerati , Semprasert Namoiy , Srisawat Chatchawan , Yenchitsomanus Pa-thai
Published: November 2017

Chronic exposure of pancreatic β-cells to high glucose levels results in β-cell dysfunction and death. These effects can be protected by estrogen. The local pancreatic renin-angiotensin system (RAS) has been shown as a novel pathological pathway of high-glucose-induced cell death. The effect of estrogen on pancreatic RAS is still unknown. This study examines whether estrogen protects against pancreatic β-cell death caused by glucotoxicity via a decrease in the pancreatic β-cell RAS pathway. When INS-1 cells were cultured in a high glucose medium, cell death was significantly higher than when the cells were cultured in a basal glucose medium; similarly, there were also higher levels of AGTR1 and p47
ph
°
x
mRNA, and protein expression. Moreover, the addition of 10−8 M 17β-estradiol to INS-1 cells cultured in a high glucose medium markedly reduced cell death, AGTR1 and p47
ph
°
x
mRNA levels, and protein expression. Similar results were demonstrated in the pancreatic islets. The presence of 10−8 M 17β-estradiol, losartan, or a combination of both, in a high glucose medium had similar levels of reduction of p47
ph
°
x
mRNA and protein expression, compared with those cultured in high glucose. Taken together, estrogen protected pancreatic β-cells from high-glucose-induced cell death by reducing the AGTR1 pathway.
Repellency of zerumbone identified in Cyperus rotundus rhizome and other constituents to Blattella germanica
Authors: Chang Kyu-Sik , Jeon Jin-Hwan , Kim Gi-Hun , Jang Chang-Won , Jeong Se-Jin , Ju Young-Ran , Ahn Young-Joon
Published: November 2017

The compounds 1,8-cineole and zerumbone (ZER) from the Cyperus rotundus rhizome along with another 11 previously identified rhizome essential oil constituents and α-humulene, which lacks the only carbonyl group present in ZER, as well as binary mixtures of ZER and seven active compounds were tested for repellency to male B. germanica. The results were compared to N,N-diethyl-3-methylbenzamide (deet). In filter-paper choice tests, ZER was the most repellent compound, and α-humulene was ineffective, which indicates that the α,β-unsaturated carbonyl group of ZER is a prerequisite component for repellency. At 81.5 μg cm−2, enhanced repellency was produced by binary mixtures of ZER and 1,8-cineole, (+)-dihydrocarvone or (R)-(+)-limonene (70:30, 50:50 and 30:70 ratios by weight). These mixtures were very effective against male B. germanica within 24 h and were more repellent than a single compound or deet alone. The optimum ZER content was determined to be more than 50%. In Ebeling choice box tests at 652.4 μg cm−2, these compounds and deet resulted in complete repellency to intact male B. germanica, while they exhibited 35–47% repellency to antennectomized male one. Mixtures formulated from the active constituents of the C. rotundus rhizome could be useful as potential repellents for controlling B. germanica.
Low resistance to chytridiomycosis in direct-developing amphibians
Authors: Mesquita Andréa F. C. , Lambertini Carolina , Lyra Mariana , Malagoli Leo R. , James Timothy Y. , Toledo Luís Felipe , Haddad Célio F. B. , Becker C. Guilherme
Published: November 2017

Host-generalist pathogens sporadically infect naive hosts, potentially triggering epizootics. The waterborne fungus Batrachochytrium dendrobatidis (Bd) is linked to declines of hundreds of amphibian species with aquatic larvae. Although several population declines and extinctions attributed to Bd have been reported among cryptic species undergoing direct development away from water, epidemiological studies focused on these terrestrial frogs are lacking. Our field data support that terrestrial direct-developing hosts are less exposed to Bd during their ontogeny than species with aquatic larvae, and thus they might lack adaptive responses against waterborne chytrids. Using controlled laboratory experiments, we exposed wild-caught amphibian species with terrestrial and aquatic life histories to Bd and found that direct developers showed more rapid increases in infection loads and experienced higher mortality rates than species with aquatic larvae. Our findings provide novel information about host responses to generalist pathogens and specifically show that our focal direct developing species have low resistance to Bd infections. Finally, our results underscore that we should not ignore Bd as a potential threat to direct developing species simply because they are less exposed to Bd in nature; instead future amphibian conservation plans should include efforts to safeguard hundreds of direct-developing amphibian species globally.
Single-shot structural analysis by high-energy X-ray diffraction using an ultrashort all-optical source
Authors: Rakowski R. , Golovin G. , O’Neal J. , Zhang J. , Zhang P. , Zhao B. , Wilson M. D. , Veale M. C. , Seller P. , Chen S. , Banerjee S. , Umstadter D. , Fuchs M.
Published: November 2017

High-energy X-rays (HEX-rays) with photon energies on order of 100 keV have attractive characteristics, such as comparably low absorption, high spatial resolution and the ability to access inner-shell states of heavy atoms. These properties are advantageous for many applications ranging from studies of bulk materials to the investigation of materials in extreme conditions. Ultrafast X-ray diffraction allows the direct imaging of atomic dynamics simultaneously on its natural time and length scale. However, using HEX-rays for ultrafast studies has been limited due to the lack of sources that can generate pulses of sufficiently short (femtosecond) duration in this wavelength range. Here we show single-crystal diffraction using ultrashort ~90 keV HEX-ray pulses generated by an all-optical source based on inverse Compton scattering. We also demonstrate a method for measuring the crystal lattice spacing in a single shot that contains only ~105 photons in a spectral bandwidth of ~50% full width at half maximum (FWHM). Our approach allows us to obtain structural information from the full X-ray spectrum. As target we use a cylindrically bent Ge crystal in Laue transmission geometry. This experiment constitutes a first step towards measurements of ultrafast atomic dynamics using femtosecond HEX-ray pulses.
High-efficiency grating-couplers: demonstration of a new design strategy
Authors: Marchetti Riccardo , Lacava Cosimo , Khokhar Ali , Chen Xia , Cristiani Ilaria , Richardson David J. , Reed Graham T. , Petropoulos Periklis , Minzioni Paolo
Published: November 2017

We present a simple and practical strategy that allows to design high-efficiency grating couplers. The technique is based on the simultaneous apodization of two structural parameters: the grating period and the fill-factor, along with the optimization of the grating coupler etching depth. Considering a 260 nm Si-thick Silicon-on-insulator platform, we numerically demonstrated a coupling efficiency of −0.8 dB (83%), well matching the experimental value of −0.9 dB (81%). Thanks to the optimized design, these results represent the best performance ever reported in the literature for SOI structures without the use of any back-reflector.
Chitosan-Graphene Oxide 3D scaffolds as Promising Tools for Bone Regeneration in Critical-Size Mouse Calvarial Defects
Authors: Hermenean Anca , Codreanu Ada , Herman Hildegard , Balta Cornel , Rosu Marcel , Mihali Ciprian Valentin , Ivan Alexandra , Dinescu Sorina , Ionita Mariana , Costache Marieta
Published: November 2017

Limited self-regenerating capacity of human skeleton makes the reconstruction of critical size bone defect a significant challenge for clinical practice. Aimed for regenerating bone tissues, this study was designed to investigate osteogenic differentiation, along with bone repair capacity of 3D chitosan (CHT) scaffolds enriched with graphene oxide (GO) in critical-sized mouse calvarial defect. Histopathological/histomorphometry and scanning electron microscopy(SEM) analysis of the implants revealed larger amount of new bone in the CHT/GO-filled defects compared with CHT alone (p < 0.001). When combined with GO, CHT scaffolds synergistically promoted the increase of alkaline phosphatase activity both in vitro and in vivo experiments. This enhanced osteogenesis was corroborated with increased expression of bone morphogenetic protein (BMP) and Runx-2 up to week 4 post-implantation, which showed that GO facilitates the differentiation of osteoprogenitor cells. Meanwhile, osteogenesis was promoted by GO at the late stage as well, as indicated by the up-regulation of osteopontin and osteocalcin at week 8 and overexpressed at week 18, for both markers. Our data suggest that CHT/GO biomaterial could represent a promising tool for the reconstruction of large bone defects, without using exogenous living cells or growth factors.
Tunneling nanotubes (TNT) mediate long-range gap junctional communication: Implications for HIV cell to cell spread
Authors: Okafo George , Prevedel Lisa , Eugenin Eliseo
Published: November 2017

Cell-to-cell communication is essen for the development of multicellular systems and is coordinated by soluble factors, exosomes, gap junction (GJ) channels, and the recently described tunneling nanotubes (TNTs). We and others have demonstrated that TNT-like structures are mostly present during pathogenic conditions, including HIV infection. However, the nature, function, and communication properties of TNTs are still poorly understood. In this manuscript, we demonstrate that TNTs induced by HIV infection have functional GJs at the ends of their membrane extensions and that TNTs mediate long-range GJ communication during HIV infection. Blocking or reducing GJ communication during HIV infection resulted in aberrant TNT cell-to-cell contact, compromising HIV spread and replication. Thus, TNTs and associated GJs are required for the efficient cell-to-cell communication and viral spread. Our data indicate that targeting TNTs/GJs may provide new therapeutic opportunities for the treatment of HIV.
Self-medication by orang-utans (Pongo pygmaeus) using bioactive properties of Dracaena cantleyi
Authors: Morrogh-Bernard H. C. , Foitová I. , Yeen Z. , Wilkin P. , de Martin R. , Rárová L. , Doležal K. , Nurcahyo W. , Olšanský M.
Published: November 2017

Animals self-medicate using a variety of plant and arthropod secondary metabolites by either ingesting them or anointing them to their fur or skin apparently to repel ectoparasites and treat skin diseases. In this respect, much attention has been focused on primates. Direct evidence for self-medication among the great apes has been limited to Africa. Here we document self-medication in the only Asian great ape, orang-utans (Pongo pygmaeus), and for the first time, to our knowledge, the external application of an anti-inflammatory agent in animals. The use of leaf extracts from Dracaena cantleyi by orang-utan has been observed on several occasions; rubbing a foamy mixture of saliva and leaf onto specific parts of the body. Interestingly, the local indigenous human population also use a poultice of these leaves for the relief of body pains. We present pharmacological analyses of the leaf extracts from this species, showing that they inhibit TNFα-induced inflammatory cytokine production (E-selectin, ICAM-1, VCAM-1 and IL-6). This validates the topical anti-inflammatory properties of this plant and provides a possible function for its use by orang-utans. This is the first evidence for the deliberate external application of substances with demonstrated bioactive potential for self-medication in great apes.
Profiling of the transcriptional response to all-trans retinoic acid in breast cancer cells reveals RARE-independent mechanisms of gene expression
Authors: Coyle Krysta Mila , Maxwell Selena , Thomas Margaret Lois , Marcato Paola
Published: November 2017

Retinoids, derivatives of vitamin A, are key physiological molecules with regulatory effects on cell differentiation, proliferation and apoptosis. As a result, they are of interest for cancer therapy. Specifically, models of breast cancer have varied responses to manipulations of retinoid signaling. This study characterizes the transcriptional response of MDA-MB-231 and MDA-MB-468 breast cancer cells to retinaldehyde dehydrogenase 1A3 (ALDH1A3) and all-trans retinoic acid (atRA). We demonstrate limited overlap between ALDH1A3-induced gene expression and atRA-induced gene expression in both cell lines, suggesting that the function of ALDH1A3 in breast cancer progression extends beyond its role as a retinaldehyde dehydrogenase. Our data reveals divergent transcriptional responses to atRA, which are largely independent of genomic retinoic acid response elements (RAREs) and consistent with the opposing responses of MDA-MB-231 and MDA-MB-468 to in vivo atRA treatment. We identify transcription factors associated with each gene set. Manipulation of the IRF1 transcription factor demonstrates that it is the level of atRA-inducible and epigenetically regulated transcription factors that determine expression of target genes (e.g. CTSS, cathepsin S). This study provides a paradigm for complex responses of breast cancer models to atRA treatment, and illustrates the need to characterize RARE-independent responses to atRA in a variety of models.
Investigating quantum metrology in noisy channels
Authors: Falaye B. J. , Adepoju A. G. , Aliyu A. S. , Melchor M. M. , Liman M. S. , Oluwadare O. J. , González-Ramírez M. D. , Oyewumi K. J.
Published: November 2017

Quantum entanglement lies at the heart of quantum information and quantum metrology. In quantum metrology, with a colossal amount of quantum Fisher information (QFI), entangled systems can be ameliorated to be a better resource scheme. However, noisy channels affect the QFI substantially. This research work seeks to investigate how QFI of N-qubit Greenberger-Horne-Zeilinger (GHZ) state is affected when subjected to decoherence channels: bit-phase flip (BPF) and generalize amplitude damping (GAD) channels, which can be induced experimentally. We determine the evolution under these channels, deduce the eigenvalues, and then derive the QFI. We found that when there is no interaction with the environment, the Heisenberg limit can be achieved via rotations along the z direction. It has been shown that in BPF channel, the maximal mean QFI of the N-qubit GHZ state ($${\bar{F}}_{max}$$

F
¯

m
a
x

) dwindles as decoherence rate (p
B
) increases due to flow of information from the system to the environment, until p
B
 = 0.5, then revives to form a symmetric around p
B
 = 0.5. Thus, p
B
 > 0.5 leads to a situation where more noise yields more efficiency. We found that in GAD channel, at finite temperature, QFIs decay more rapidly than at zero temperature. Our results also reveal that QFI can be enhanced by adjusting the temperature of the environment.
Study of the lithium diffusion properties and high rate performance of TiNb6O17 as an anode in lithium secondary battery
Authors: Lee Yong-Seok , Ryu Kwang-Sun
Published: November 2017

TiNb6O17 and TiNb2O7 were synthesized using a solid-state method. The techniques were used to assess the electrochemical performance and lithium diffusion kinetics of TiNb6O17 related to the unit cell volume with TiNb2O7. The charge-discharge curves and cyclic voltammetry revealed TiNb6O17 to have a similar redox potential to TiNb2O7 as well as a high discharge capacity. The rate performance of TiNb6O17 was measured using a rate capability test. SSCV and EIS showed that TiNb6O17 had higher lithium diffusion coefficients during the charging. From GITT, the lithium diffusion coefficients at the phase transition region showed the largest increase from TiNb2O7 to TiNb6O17.
Solution structure and interaction with copper in vitro and in living cells of the first BIR domain of XIAP
Authors: Hou Meng-Meng , Polykretis Panagis , Luchinat Enrico , Wang Xiao , Chen Shen-Na , Zuo Hui-Hui , Yang Yin , Chen Jia-Liang , Ye Yansheng , Li Conggang , Banci Lucia , Su Xun-Cheng
Published: November 2017

The X-chromosome linked inhibitor of apoptosis (XIAP) is a multidomain metalloprotein involved in caspase inhibition and in copper homeostasis. It contains three zinc-binding baculoviral IAP repeats (BIR) domains, which are responsible for caspase interaction. Recently, it has been suggested that the BIR domains can bind copper, however high resolution data on such interaction is missing. Here we characterize by NMR the structural properties of BIR1 in solution, and the effects of its interaction with copper both in vitro and in physiological environments. BIR1 is dimeric in solution, consistent with the X-ray structure. Cysteine 12, located in the unfolded N-terminal region, has a remarkably low redox potential, and is prone to oxidation even in reducing physiological environments. Interaction of BIR1 with copper(II) results in the oxidation of cysteine 12, with the formation of either an intermolecular disulfide bond between two BIR1 molecules or a mixed disulfide bond with glutathione, whereas the zinc binding site is not affected by the interaction.
Unbiased Quantitative Proteomics Reveals a Crucial Role of the Allergen Context for the Activation of Human Dendritic Cells
Authors: Strasser L. , Dang H.-H. , Schwarz H. , Asam C. , Ferreira F. , Horejs-Hoeck J. , Huber C. G.
Published: November 2017

Worldwide, more than 1 billion people suffer from allergic diseases. However, until now it is not fully understood how certain proteins can induce allergic immune responses, while others cannot. Studies suggest that allergenicity is a process not only determined by properties of the allergen itself but also by costimulatory factors, that are not classically associated with allergic reactions. To investigate the allergenicity of the major birch pollen allergen Bet v 1 and the impact of adjuvants associated with pollen, e.g. lipopolysaccharide (LPS), we performed quantitative proteome analysis to study the activation of monocyte-derived dendritic cells (moDCs). Thus, we treated cells with birch pollen extract (BPE), recombinant Bet v 1, and LPS followed by proteomic profiling via high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) using isobaric labelling. Enrichment and pathway analysis revealed the influence of regulated proteins especially in cytokine signalling and dendritic cell activation. We found highly regulated, but differentially expressed proteins after treatment with BPE and LPS, whereas the cellular response to Bet v 1 was limited. Our findings lead to the conclusion that Bet v 1 needs a specific “allergen context” involving cofactors apart from LPS to induce an immune response in human moDCs.
Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells
Authors: Morita Ken , Noura Mina , Tokushige Chieko , Maeda Shintaro , Kiyose Hiroki , Kashiwazaki Gengo , Taniguchi Junichi , Bando Toshikazu , Yoshida Kenichi , Ozaki Toshifumi , Matsuo Hidemasa , Ogawa Seishi , Liu Pu Paul , Nakahata Tatsutoshi , Sugiyama Hiroshi , Adachi Souichi , Kamikubo Yasuhiko
Published: November 2017

Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-β (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.
Interaction of Synthetic Human SLURP-1 with the Nicotinic Acetylcholine Receptors
Authors: Durek Thomas , Shelukhina Irina V. , Tae Han-Shen , Thongyoo Panumart , Spirova Ekaterina N. , Kudryavtsev Denis S. , Kasheverov Igor E. , Faure Grazyna , Corringer Pierre-Jean , Craik David J. , Adams David J. , Tsetlin Victor I.
Published: November 2017

Human SLURP-1 is a secreted protein of the Ly6/uPAR/three-finger neurotoxin family that co-localizes with nicotinic acetylcholine receptors (nAChRs) and modulates their functions. Conflicting biological activities of SLURP-1 at various nAChR subtypes have been based on heterologously produced SLURP-1 containing N- and/or C-terminal extensions. Here, we report the chemical synthesis of the 81 amino acid residue human SLURP-1 protein, characterization of its 3D structure by NMR, and its biological activity at nAChR subtypes. Radioligand assays indicated that synthetic SLURP-1 did not compete with [125I]-α-bungarotoxin (α-Bgt) binding to human neuronal α7 and Torpedo californica muscle-type nAChRs, nor to mollusk acetylcholine binding proteins (AChBP). Inhibition of human α7-mediated currents only occurred in the presence of the allosteric modulator PNU120596. In contrast, we observed robust SLURP-1 mediated inhibition of human α3β4, α4β4, α3β2 nAChRs, as well as human and rat α9α10 nAChRs. SLURP-1 inhibition of α9α10 nAChRs was accentuated at higher ACh concentrations, indicating an allosteric binding mechanism. Our results are discussed in the context of recent studies on heterologously produced SLURP-1 and indicate that N-terminal extensions of SLURP-1 may affect its activity and selectivity on its targets. In this respect, synthetic SLURP-1 appears to be a better probe for structure-function studies.
BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency
Authors: Lu Panpan , Shen Yinzhong , Yang He , Wang Yanan , Jiang Zhengtao , Yang Xinyi , Zhong Yangcheng , Pan Hanyu , Xu Jianqing , Lu Hongzhou , Zhu Huanzhang
Published: November 2017

Persistent latent reservoir in resting CD4+ T cells is a major obstacle in curing HIV-1 infection. Effective strategies for eradication of the HIV-1 reservoir are urgently needed. We report here for the first time that two BET inhibitors, RVX-208, which has entered phase II clinical trials for diverse cardiovascular disorders, and PFI-1, which has been widely studied in oncology, can reactivate HIV-1 from latency. RVX-208 and PFI-1 treatment alone or in combination with other latency reversing agents efficiently reactivated HIV-1 transcription through an up-regulation of P-TEFb by increasing CDK9 Thr-186 phosphorylation in latently infected Jurkat T cells in vitro. The two BET inhibitors also reactivated HIV-1 transcription in cART treated patient-derived resting CD4+ T cells ex vivo, without influence on global immune cell activation. Our findings, in combination with previous reports, further confirm that BET inhibitors are a group of leading compounds for combating HIV-1 latency for viral eradication.
Viscous Fingering in Multiport Hele Shaw Cell for Controlled Shaping of Fluids
Authors: Islam Tanveer ul , Gandhi Prasanna S.
Published: November 2017

The pursuit of mimicking complex multiscale systems has been a tireless effort with many successes but a daunting task ahead. A new perspective to engineer complex cross-linked meshes and branched/tree-like structures at different scales is presented here. Control over Saffman-Taylor instability which otherwise randomly rearranges viscous fluid in a ‘lifted Hele-Shaw cell’ is proposed for the same. The proposed control employs multiple-ports or source-holes in this cell, to spontaneously shape a stretched fluid film into a network of well defined webs/meshes and ordered multiscale tree-like patterns. Use of multiple ports enables exercising strong control to fabricate such structures, in a robust and repeated fashion, which otherwise are completely non-characteristic to viscous fingering process. The proposed technique is capable of fabricating spontaneously families of wide variety of structures over micro and very large scale in a period of few seconds. Thus the proposed method forms a solid foundation to new pathways for engineering multiscale structures for several scientific applications including efficient gas exchange, heat transport, tissue engineering, organ-on-chip, and so on. Proposal of multi-port Hele-Shaw cell also opens new avenues for investigation of complex multiple finger interactions resulting in interesting fluid patterns.
Improved Detection of Cytokines Produced by Invariant NKT Cells
Authors: Sag Duygu , Özkan Müge , Kronenberg Mitchell , Wingender Gerhard
Published: November 2017

Invariant Natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after in vivo activation, allowing for the direct detection of a number of cytokines directly ex vivo. However, for some cytokines this approach is suboptimal. Here, we report technical variations that allow the improved detection of IL-4, IL-10, IL-13 and IL-17A ex vivo. Furthermore, we describe an alternative approach for stimulation of iNKT cells in vitro that allows a significantly improved detection of cytokines produced by iNKT cells. Together, these protocols allow the detection of iNKT cell cytokines ex vivo and in vitro with increased sensitivity.
Roller-Induced Bundling of Long Silver Nanowire Networks for Strong Interfacial Adhesion, Highly Flexible, Transparent Conductive Electrodes
Authors: Chen Yan-Ren , Hong Chien-Chong , Liou Tong-Miin , Hwang Kuo Chu , Guo Tzung-Fang
Published: November 2017

Silver nanowires (AgNWs) have been the most promising electrode materials for fabrication of flexible transparent touch panel, displays and many other electronics because of their excellent electrical properties, cost effectiveness, synthesis scalability, and suitability for mass production. Although a few literature reports have described the use of short Ag NWs in fabrication of randomly oriented Ag NW network-based electrode, their electrical conductivities are still far lower than that of Ag films. So far, no any literature report was able to provide any simple solution to fabrication of large-area and mass-manufactural ability to address the issues, such as, conductivity, transparency, electrical current withstand, bending stability, and interfacial adhesion. In the current work, we provide a simple solution to conquer the above-mentioned challenges, and report the development of long Ag NW bundle network electrodes on large area PET films that were coated, aligned, and bundled quickly and simply using a steel roller. Our developed AgNWs-bundle networks had superior performance in optoelectronic properties (sheet resistance 5.8 Ω sq−1; optical transmittance 89% at 550 nm wavelength), electrical current withstand up to 500 mA, and bending stability over 5000 bending cycles, and strong interfacial adhesion.
HIDEEP: a systems approach to predict hormone impacts on drug efficacy based on effect paths
Authors: Kwon Mijin , Jung Jinmyung , Yu Hasun , Lee Doheon
Published: November 2017

Experimental evidence has shown that some of the human endogenous hormones significantly affect drug efficacy. Since hormone status varies with individual physiological states, it is essential to understand the interplay of hormones and drugs for precision medicine. Here, we developed an in silico method to predict interactions between 283 human endogenous hormones and 590 drugs for 20 diseases including cancers and non-cancer diseases. We extracted hormone effect paths and drug effect paths from a large-scale molecular network that contains protein interactions, transcriptional regulations, and signaling interactions. If two kinds of effect paths for a hormone-drug pair intersect closely, we expect that the influence of the hormone on the drug efficacy is significant. It has been shown that the proposed method correctly distinguishes hormone-drug pairs with known interactions from random pairs in blind experiments. In addition, the method can suggest underlying interaction mechanisms at the molecular level so that it helps us to better understand the interplay of hormones and drugs.