bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rosmarinic acid: modes of action, medicinal values and health benefits
Authors: Alagawany Mahmoud , Abd El-Hack Mohamed Ezzat , Farag Mayada Ragab , Gopi Marappan , Karthik Kumaragurubaran , Malik Yashpal Singh , Dhama Kuldeep 
Published: November 2017

AbstractThe supplementation of livestock rations with herbs containing bioactive components, such as rosmarinic acid (RA), have shown promising results as a natural feed additive in promoting growth, productive and reproductive performance, feed utilization, fertility, anti-oxidant status and immunologic indices. Furthermore, RA reportedly reduces the risks of various animal diseases and mitigates side effects of chemical and synthetic drugs. RA is a natural polyphenol present in several Lamiaceae herbs like Perilla frutescens, and RA is becoming an integral component of animal nutrition as it counters the effect of reactive oxygen species induced in the body as a consequence of different kinds of stressors. Studies have further ascertained the capability of RA to work as an anti-microbial, immunomodulatory, anti-diabetic, anti-allergic, anti-inflammatory, hepato- and renal-protectant agent, as well as to have beneficial effects during skin afflictions. Additionally, RA is favored in meat industries due to enhancing the quality of meat products by reportedly improving shelf-life and imparting desirable flavor. This review describes the beneficial applications and recent findings with RA, including its natural sources, modes of action and various useful applications in safeguarding livestock health as well as important aspects of human health.
Japan's Womenomics Diplomacy: Fighting Stigma and Constructing ODA Leadership on Gender Equality
Authors: COLEMAN LIV 
Published: November 2017

AbstractUnder conservative Prime Minister Abe Shinzo, Japan has embarked upon a high profile ‘Womenomics’ foreign policy agenda to highlight Japan's official development assistance (ODA) contributions to women's empowerment worldwide. This paper examines the puzzle of why such an avowedly conservative government would pursue a feminist foreign policy agenda. The paper finds that Japan's Womenomics diplomacy cannot be explained simply by materialist or domestic political explanations, but is best understood as a strategic campaign stemming from elite concern about Japan's national identity and esteem about its status in the world. Through Womenomics diplomacy, Japan's Ministry of Foreign Affairs attempts to construct Japan as a leader on women's rights and gender equality in response to the twin stigmas of Japan's treatment of wartime ‘comfort women’ and perennial low rankings on international indexes of gender equality.
Hit-and-run epigenetic editing prevents senescence entry in primary breast cells from healthy donors
Authors: Saunderson Emily A. , Stepper Peter , Gomm Jennifer J. , Hoa Lily , Morgan Adrienne , Allen Michael D. , Jones J. Louise , Gribben John G. , Jurkowski Tomasz P. , Ficz Gabriella 
Published: November 2017

AbstractAberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest. Our data show that the key driver of this phenotype is repression of CDKN2A transcript p16 where myoepithelial cells harbour cancer-like gene expression but do not exhibit anchorage-independent growth. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, which may facilitate tumour initiation.
The multiple antibiotic resistance operon of enteric bacteria controls DNA repair and outer membrane integrity
Authors: Sharma Prateek , Haycocks James R. J. , Middlemiss Alistair D. , Kettles Rachel A. , Sellars Laura E. , Ricci Vito , Piddock Laura J. V. , Grainger David C. 
Published: November 2017

AbstractThe multiple antibiotic resistance (mar) operon of Escherichia coli is a paradigm for chromosomally encoded antibiotic resistance in enteric bacteria. The locus is recognised for its ability to modulate efflux pump and porin expression via two encoded transcription factors, MarR and MarA. Here we map binding of these regulators across the E. coli genome and identify an extensive mar regulon. Most notably, MarA activates expression of genes required for DNA repair and lipid trafficking. Consequently, the mar locus reduces quinolone-induced DNA damage and the ability of tetracyclines to traverse the outer membrane. These previously unrecognised mar pathways reside within a core regulon, shared by most enteric bacteria. Hence, we provide a framework for understanding multidrug resistance, mediated by analogous systems, across the Enterobacteriaceae. Transcription factors MarR and MarA confer multidrug resistance in enteric bacteria by modulating efflux pump and porin expression. Here, Sharma et al. show that MarA also upregulates genes required for lipid trafficking and DNA repair, thus reducing antibiotic entry and quinolone-induced DNA damage.
Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer’s disease-like pathology
Authors: Nuriel Tal , Angulo Sergio L. , Khan Usman , Ashok Archana , Chen Qiuying , Figueroa Helen Y. , Emrani Sheina , Liu Li , Herman Mathieu , Barrett Geoffrey , Savage Valerie , Buitrago Luna , Cepeda-Prado Efrain , Fung Christine , Goldberg Eliana , Gross Steven S. , Hussaini S. Abid , Moreno Herman , Small Scott A. , Duff Karen E. 
Published: November 2017

AbstractThe ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer’s disease (AD). However, the reason APOE4 is associated with increased AD risk remains a source of debate. Neuronal hyperactivity is an early phenotype in both AD mouse models and in human AD, which may play a direct role in the pathogenesis of the disease. Here, we have identified an APOE4-associated hyperactivity phenotype in the brains of aged APOE mice using four complimentary techniques—fMRI, in vitro electrophysiology, in vivo electrophysiology, and metabolomics—with the most prominent hyperactivity occurring in the entorhinal cortex. Further analysis revealed that this neuronal hyperactivity is driven by decreased background inhibition caused by reduced responsiveness of excitatory neurons to GABAergic inhibitory inputs. Given the observations of neuronal hyperactivity in prodromal AD, we propose that this APOE4-driven hyperactivity may be a causative factor driving increased risk of AD among APOE4 carriers.
RNA editing by ADAR1 leads to context-dependent transcriptome-wide changes in RNA secondary structure
Authors: Solomon Oz , Di Segni Ayelet , Cesarkas Karen , Porath Hagit T. , Marcu-Malina Victoria , Mizrahi Orel , Stern-Ginossar Noam , Kol Nitzan , Farage-Barhom Sarit , Glick-Saar Efrat , Lerenthal Yaniv , Levanon Erez Y. , Amariglio Ninette , Unger Ron , Goldstein Itamar , Eyal Eran , Rechavi Gidi 
Published: November 2017

AbstractAdenosine deaminase acting on RNA 1 (ADAR1) is the master RNA editor, catalyzing the deamination of adenosine to inosine. RNA editing is vital for preventing abnormal activation of cytosolic nucleic acid sensing pathways by self-double-stranded RNAs. Here we determine, by parallel analysis of RNA secondary structure sequencing (PARS-seq), the global RNA secondary structure changes in ADAR1 deficient cells. Surprisingly, ADAR1 silencing resulted in a lower global double-stranded to single-stranded RNA ratio, suggesting that A-to-I editing can stabilize a large subset of imperfect RNA duplexes. The duplexes destabilized by editing are composed of vastly complementary inverted Alus found in untranslated regions of genes performing vital biological processes, including housekeeping functions and type-I interferon responses. They are predominantly cytoplasmic and generally demonstrate higher ribosomal occupancy. Our findings imply that the editing effect on RNA secondary structure is context dependent and underline the intricate regulatory role of ADAR1 on global RNA secondary structure.
Virtual photons in the ground state of a dissipative system
Authors: De Liberato Simone 
Published: November 2017

AbstractMuch of the novel physics predicted to be observable in the ultrastrong light–matter coupling regime rests on the hybridisation between states with different numbers of excitations, leading to a population of virtual photons in the system’s ground state. In this article, exploiting an exact diagonalisation approach, we derive both analytical and numerical results for the population of virtual photons in presence of arbitrary losses. Specialising our results to the case of Lorentzian resonances we then show that the virtual photon population is only quantitatively affected by losses, even when those become the dominant energy scale. Our results demonstrate most of the ultrastrong-coupling phenomenology can be observed in loss-dominated systems which are not even in the standard strong coupling regime. We thus open the possibility to investigate ultrastrong-coupling physics to platforms that were previously considered unsuitable due to their large losses.
Mapping functional diversity from remotely sensed morphological and physiological forest traits
Authors: Schneider Fabian D. , Morsdorf Felix , Schmid Bernhard , Petchey Owen L. , Hueni Andreas , Schimel David S. , Schaepman Michael E. 
Published: November 2017

AbstractAssessing functional diversity from space can help predict productivity and stability of forest ecosystems at global scale using biodiversity–ecosystem functioning relationships. We present a new spatially continuous method to map regional patterns of tree functional diversity using combined laser scanning and imaging spectroscopy. The method does not require prior taxonomic information and integrates variation in plant functional traits between and within plant species. We compare our method with leaf-level field measurements and species-level plot inventory data and find reasonable agreement. Morphological and physiological diversity show consistent change with topography and soil, with low functional richness at a mountain ridge under specific environmental conditions. Overall, functional richness follows a logarithmic increase with area, whereas divergence and evenness are scale invariant. By mapping diversity at scales of individual trees to whole communities we demonstrate the potential of assessing functional diversity from space, providing a pathway only limited by technological advances and not by methodology.
An unusual endo-selective C-H hydroarylationof norbornene by the Rh(I)-catalyzed reactionof benzamides
Authors: Shibata Kaname , Natsui Satoko , Tobisu Mamoru , Fukumoto Yoshiya , Chatani Naoto 
Published: November 2017

AbstractHydroarylation is an environmentally attractive strategy which incorporates all of the atoms contained in the substrates into the desired products. Almost all the hydroarylations of norbornene reported to date involve an exo-selective reaction. Here we show the endo-selective hydroarylation of norbornene in the Rh(I)-catalyzed reaction of aromatic amides. The addition of sterically bulky carboxylic acids enhances the endo-selectivity of the reaction. The results of deuterium-labeling experiments show that both the ortho-carbon and the ortho-hydrogen atoms of aromatic amides were attached to the same carbon atom of the norbornane skeleton in the hydroarylation product. These results clearly suggest that hydrometalation or carbometalation, which are commonly accepted mechanisms for the catalytic hydroarylation of C–H bonds, are not involved as the key step in the present reaction, and suggest that the reaction involves a rhodium carbene complex generated from norbornene as the key intermediate.
Highly selective nickel-catalyzed gem-difluoropropargylation of unactivated alkylzinc reagents
Authors: An Lun , Xu Chang , Zhang Xingang 
Published: November 2017

AbstractIn spite of the important applications of difluoroalkylated molecules in medicinal chemistry, to date, the reaction of difluoroalkylating reagents with unactivated, aliphatic substrates through a controllable manner remains challenging and has not been reported. Here we describe an efficient nickel-catalyzed cross-coupling of unactivated alkylzinc reagen\ts with gem-difluoropropargyl bromides. The reaction proceeds under mild reaction conditions with high efficiency and excellent regiochemical selectivity. Transformations of the resulting difluoroalkylated alkanes lead to a variety of biologically active molecules, providing a facile route for applications in drug discovery and development. Preliminary mechanistic studies reveal that an alkyl nickel intermediate [Ni(tpy)alkyl] (tpy, terpyridine) is involved in the catalytic cycle.
Thermostable exoshells fold and stabilize recombinant proteins
Authors: Deshpande Siddharth , Masurkar Nihar D. , Girish Vallerinteavide Mavelli , Desai Malan , Chakraborty Goutam , Chan Juliana M. , Drum Chester L. 
Published: November 2017

AbstractThe expression and stabilization of recombinant proteins is fundamental to basic and applied biology. Here we have engineered a thermostable protein nanoparticle (tES) to improve both expression and stabilization of recombinant proteins using this technology. tES provides steric accommodation and charge complementation to green fluorescent protein (GFPuv), horseradish peroxidase (HRPc), and Renilla luciferase (rLuc), improving the yields of functional in vitro folding by ~100-fold. Encapsulated enzymes retain the ability to metabolize small-molecule substrates, presumably via four 4.5-nm pores present in the tES shell. GFPuv exhibits no spectral shifts in fluorescence compared to a nonencapsulated control. Thermolabile proteins internalized by tES are resistant to thermal, organic, chaotropic, and proteolytic denaturation and can be released from the tES assembly with mild pH titration followed by proteolysis.
Nanopore electric snapshots of an RNA tertiary folding pathway
Authors: Zhang Xinyue , Zhang Dong , Zhao Chenhan , Tian Kai , Shi Ruicheng , Du Xiao , Burcke Andrew J. , Wang Jing , Chen Shi-Jie , Gu Li-Qun 
Published: November 2017

AbstractThe chemical properties and biological mechanisms of RNAs are determined by their tertiary structures. Exploring the tertiary structure folding processes of RNA enables us to understand and control its biological functions. Here, we report a nanopore snapshot approach combined with coarse-grained molecular dynamics simulation and master equation analysis to elucidate the folding of an RNA pseudoknot structure. In this approach, single RNA molecules captured by the nanopore can freely fold from the unstructured state without constraint and can be programmed to terminate their folding process at different intermediates. By identifying the nanopore signatures and measuring their time-dependent populations, we can “visualize” a series of kinetically important intermediates, track the kinetics of their inter-conversions, and derive the RNA pseudoknot folding pathway. This approach can potentially be developed into a single-molecule toolbox to investigate the biophysical mechanisms of RNA folding and unfolding, its interactions with ligands, and its functions.
Optically-controlled long-term storage and release of thermal energy in phase-change materials
Authors: Han Grace G. D. , Li Huashan , Grossman Jeffrey C. 
Published: November 2017

AbstractThermal energy storage offers enormous potential for a wide range of energy technologies. Phase-change materials offer state-of-the-art thermal storage due to high latent heat. However, spontaneous heat loss from thermally charged phase-change materials to cooler surroundings occurs due to the absence of a significant energy barrier for the liquid–solid transition. This prevents control over the thermal storage, and developing effective methods to address this problem has remained an elusive goal. Herein, we report a combination of photo-switching dopants and organic phase-change materials as a way to introduce an activation energy barrier for phase-change materials solidification and to conserve thermal energy in the materials, allowing them to be triggered optically to release their stored latent heat. This approach enables the retention of thermal energy (about 200 J g−1) in the materials for at least 10 h at temperatures lower than the original crystallization point, unlocking opportunities for portable thermal energy storage systems.
Volcanism in slab tear faults is larger than in island-arcs and back-arcs
Authors: Cocchi Luca , Passaro Salvatore , Tontini Fabio Caratori , Ventura Guido 
Published: November 2017

AbstractSubduction-transform edge propagators are lithospheric tears bounding slabs and back-arc basins. The volcanism at these edges is enigmatic because it is lacking comprehensive geological and geophysical data. Here we present bathymetric, potential-field data, and direct observations of the seafloor on the 90 km long Palinuro volcanic chain overlapping the E-W striking tear of the roll-backing Ionian slab in Southern Tyrrhenian Sea. The volcanic chain includes arc-type central volcanoes and fissural, spreading-type centers emplaced along second-order shears. The volume of the volcanic chain is larger than that of the neighbor island-arc edifices and back-arc spreading center. Such large volume of magma is associated to an upwelling of the isotherms due to mantle melts upraising from the rear of the slab along the tear fault. The subduction-transform edge volcanism focuses localized spreading processes and its magnitude is underestimated. This volcanism characterizes the subduction settings associated to volcanic arcs and back-arc spreading centers.
Ist1 regulates ESCRT-III assembly and function during multivesicular endosome biogenesis in Caenorhabditis elegans embryos
Authors: Frankel E. B. , Shankar Raakhee , Moresco James J. , Yates John R. , Volkmann Niels , Audhya Anjon 
Published: November 2017

AbstractDegradation of most integral membrane proteins is directed by the endosomal sorting complex required for transport (ESCRT) machinery, which selectively targets ubiquitin-modified cargoes into intralumenal vesicles (ILVs) within multivesicular endosomes (MVEs). To better understand the mechanisms underlying ESCRT-mediated formation of ILVs, we exploited the rapid, de novo biogenesis of MVEs during the oocyte-to-embryo transition in C. elegans. In contrast to previous models suggesting that ILVs form individually, we demonstrate that they remain tethered to one another subsequent to internalization, arguing that they bud continuously from stable subdomains. In addition, we show that membrane bending and ILV formation are directed specifically by the ESCRT-III complex in vivo in a manner regulated by Ist1, which promotes ESCRT-III assembly and inhibits the incorporation of upstream ESCRT components into ILVs. Our findings underscore essential actions for ESCRT-III in membrane remodeling, cargo selection, and cargo retention, which act repetitively to maximize the rate of ILV formation.
Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge
Authors: Wen Jinsheng , Elong Ngono Annie , Regla-Nava Jose Angel , Kim Kenneth , Gorman Matthew J. , Diamond Michael S. , Shresta Sujan 
Published: November 2017

AbstractZika virus (ZIKV) and dengue virus (DENV) are antigenically related flaviviruses that share cross-reactivity in antibody and T cell responses, and co-circulate in increasing numbers of countries. Whether pre-existing DENV immunity can cross-protect or enhance ZIKV infection during sequential infection of the same host is unknown. Here, we show that DENV-immuneIfnar1−/−or wild-type C57BL/6 mice infected with ZIKV have cross-reactive immunity to subsequent ZIKV infection and pathogenesis. Adoptive transfer and cell depletion studies demonstrate that DENV-immune CD8+T cells predominantly mediate cross-protective responses to ZIKV. In contrast, passive transfer studies suggest that DENV-immune serum does not protect against ZIKV infection. Thus, CD8+T cell immunity generated during primary DENV infection can confer protection against secondary ZIKV infection in mice. Further optimization of current DENV vaccines for T cell responses might confer cross-protection and prevent antibody-mediated enhancement of ZIKV infection.
Atomically-precise colloidal nanoparticles of cerium dioxide
Authors: Mitchell Kylie J. , Abboud Khalil A. , Christou George 
Published: November 2017

AbstractSynthesis of truly monodisperse nanoparticles and their structural characterization to atomic precision are important challenges in nanoscience. Success has recently been achieved for metal nanoparticles, particularly Au, with diameters up to 3 nm, the size regime referred to as nanoclusters. In contrast, families of atomically precise metal oxide nanoparticles are currently lacking, but would have a major impact since metal oxides are of widespread importance for their magnetic, catalytic and other properties. One such material is colloidal CeO2 (ceria), whose applications include catalysis, new energy technologies, photochemistry, and medicine, among others. Here we report a family of atomically precise ceria nanoclusters with ultra-small dimensions up to ~1.6 nm (~100 core atoms). X-ray crystallography confirms they have the fluorite structure of bulk CeO2, and identifies surface features, H+ binding sites, Ce3+ locations, and O vacancies on (100) facets. Monodisperse ceria nanoclusters now permit investigation of their properties as a function of exact size, surface morphology, and Ce3+:Ce4+ composition.
Development of a genetic sensor that eliminates p53 deficient cells
Authors: Mircetic Jovan , Dietrich Antje , Paszkowski-Rogacz Maciej , Krause Mechthild , Buchholz Frank 
Published: November 2017

AbstractThe TP53 gene fulfills a central role in protecting cells from genetic insult. Given this crucial role it might be surprising that p53 itself is not essential for cell survival. Indeed, TP53 is the single most mutated gene across different cancer types. Thus, both a theoretical and a question of significant practical applicability arise: can cells be programmed to make TP53 an essential gene? Here we present a genetic p53 sensor, in which the loss of p53 is coupled to the rise of HSV-TK expression. We show that the sensor can distinguish both p53 knockout and cells expressing a common TP53 cancer mutation from otherwise isogenic TP53 wild-type cells. Importantly, the system is sensitive enough to specifically target TP53 loss-of-function cells with the HSV-TK pro-drug Ganciclovir both in vitro and in vivo. Our work opens new ways to programming cell intrinsic transformation protection systems that rely on endogenous components.