bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity
Authors: Zhang Bing , Zhou Wen-Jie , Gu Chun-Jie , Wu Ke , Yang Hui-Li , Mei Jie , Yu Jia-Jun , Hou Xiao-Fan , Sun Jian-Song , Xu Feng-Yuan , Li Da-Jin , Jin Li-Ping , Li Ming-Qing 
Published: May 2018

AbstractEndometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.
The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/β-catenin signalling
Authors: Zhang Chong , Xiang Tingxiu , Li Shuman , Ye Lin , Feng Yixiao , Pei Lijiao , Li Lili , Wang Xiangyu , Sun Ran , Ren Guosheng , Tao Qian 
Published: May 2018

AbstractZinc finger proteins (ZFPs) are the largest transcription factor family in mammals. About one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs and involved in the regulation of cell differentiation/proliferation/apoptosis and neoplastic transformation. We recently identified ZNF382 as a novel KRAB-ZFP epigenetically inactivated in multiple cancers due to frequent promoter CpG methylation. However, its epigenetic alterations, biological functions/mechanism and clinical significance in oesophageal squamous cell carcinoma (ESCC) are still unknown. Here, we demonstrate that ZNF382 expression was suppressed in ESCC due to aberrant promoter methylation, but highly expressed in normal oesophagus tissues. ZNF382 promoter methylation is correlated with ESCC differentiation levels. Restoration of ZNF382 expression in silenced ESCC cells suppressed tumour cell proliferation and metastasis through inducing cell apoptosis. Importantly, ZNF382 suppressed Wnt/β-catenin signalling and downstream target gene expression, likely through binding directly to FZD1 and DVL2 promoters. In summary, our findings demonstrate that ZNF382 functions as a bona fide tumour suppressor inhibiting ESCC pathogenesis through inhibiting the Wnt/β-catenin signalling pathway.
Bacterial encapsulins as orthogonal compartments for mammalian cell engineering
Authors: Sigmund Felix , Massner Christoph , Erdmann Philipp , Stelzl Anja , Rolbieski Hannes , Desai Mitul , Bricault Sarah , Wörner Tobias P. , Snijder Joost , Geerlof Arie , Fuchs Helmut , Hrabĕ de Angelis Martin , Heck Albert J. R. , Jasanoff Alan , Ntziachristos Vasilis , Plitzko Jürgen , Westmeyer Gil G. 
Published: May 2018

AbstractWe genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB,C) results in efficient iron sequestration producing substantial contrast by magnetic resonance imaging (MRI) and allowing for magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells are also excellent genetically encoded reporters for electron microscopy (EM). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.
Phenotypic diversification by enhanced genome restructuring after induction of multiple DNA double-strand breaks
Authors: Muramoto Nobuhiko , Oda Arisa , Tanaka Hidenori , Nakamura Takahiro , Kugou Kazuto , Suda Kazuki , Kobayashi Aki , Yoneda Shiori , Ikeuchi Akinori , Sugimoto Hiroki , Kondo Satoshi , Ohto Chikara , Shibata Takehiko , Mitsukawa Norihiro , Ohta Kunihiro 
Published: May 2018

AbstractDNA double-strand break (DSB)-mediated genome rearrangements are assumed to provide diverse raw genetic materials enabling accelerated adaptive evolution; however, it remains unclear about the consequences of massive simultaneous DSB formation in cells and their resulting phenotypic impact. Here, we establish an artificial genome-restructuring technology by conditionally introducing multiple genomic DSBs in vivo using a temperature-dependent endonuclease TaqI. Application in yeast and Arabidopsis thaliana generates strains with phenotypes, including improved ethanol production from xylose at higher temperature and increased plant biomass, that are stably inherited to offspring after multiple passages. High-throughput genome resequencing revealed that these strains harbor diverse rearrangements, including copy number variations, translocations in retrotransposons, and direct end-joinings at TaqI-cleavage sites. Furthermore, large-scale rearrangements occur frequently in diploid yeasts (28.1%) and tetraploid plants (46.3%), whereas haploid yeasts and diploid plants undergo minimal rearrangement. This genome-restructuring system (TAQing system) will enable rapid genome breeding and aid genome-evolution studies.
Stepwise control of host–guest interaction using a coordination polymer gel
Authors: Mukhopadhyay Rahul Dev , Das Gourab , Ajayaghosh Ayyappanpillai 
Published: May 2018

AbstractPrecise control of host–guest interaction as seen in biological processes is difficult to achieve with artificial systems. Herein we have exploited the thermodynamic benefits of a system in equilibrium to achieve controlled stepwise release and capture of cyclodextrin (guest) using a coordination polymer (Mg-CP) as the host and temperature as the stimulus. Since temperature is not a precision stimulus for artificial host–guest interaction, the present system is a distinct prototype that manifests temperature-controlled natural host–guest interaction. The described coordination polymeric host system, when incorporated into a hydrogel matrix, provides a microenvironment that facilitates the stepwise release of α-CD in response to temperature variation within a quasi-solid state. The work demonstrated here may pave the way towards thermally controlled delivery and monitoring of otherwise spectroscopically silent molecules such as cyclodextrins.
MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity
Authors: Skucha Anna , Ebner Jessica , Schmöllerl Johannes , Roth Mareike , Eder Thomas , César-Razquin Adrián , Stukalov Alexey , Vittori Sarah , Muhar Matthias , Lu Bin , Aichinger Martin , Jude Julian , Müller André C. , Győrffy Balázs , Vakoc Christopher R. , Valent Peter , Bennett Keiryn L. , Zuber Johannes , Superti-Furga Giulio , Grebien Florian 
Published: May 2018

AbstractMLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein–protein interactions of seven distantly related MLL-fusion proteins. Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia. SETD2 loss causes growth arrest and differentiation of AML cells, and leads to increased DNA damage. In addition to its role in H3K36 tri-methylation, SETD2 is required to maintain high H3K79 di-methylation and MLL-AF9-binding to critical target genes, such as Hoxa9. SETD2 loss synergizes with pharmacologic inhibition of the H3K79 methyltransferase DOT1L to induce DNA damage, growth arrest, differentiation, and apoptosis. These results uncover a dependency for SETD2 during MLL-leukemogenesis, revealing a novel actionable vulnerability in this disease.
Optical wireless link between a nanoscale antenna and a transducing rectenna
Authors: Dasgupta Arindam , Mennemanteuil Marie-Maxime , Buret Mickaël , Cazier Nicolas , Colas-des-Francs Gérard , Bouhelier Alexandre 
Published: May 2018

AbstractInitiated as a cable-replacement solution, short-range wireless power transfer has rapidly become ubiquitous in the development of modern high-data throughput networking in centimeter to meter accessibility range. Wireless technology is now penetrating a higher level of system integration for chip-to-chip and on-chip radiofrequency interconnects. However, standard CMOS integrated millimeter-wave antennas have typical size commensurable with the operating wavelength, and are thus an unrealistic solution for downsizing transmitters and receivers to the micrometer and nanometer scale. Herein, we demonstrate a light-in and electrical signal-out, on-chip wireless near-infrared link between a 220 nm optical antenna and a sub-nanometer rectifying antenna converting the transmitted optical energy into direct electrical current. The co-integration of subwavelength optical functional devices with electronic transduction offers a disruptive solution to interface photons and electrons at the nanoscale for on-chip wireless optical interconnects.
TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis
Authors: Iriondo Oihana , Liu Yarong , Lee Grace , Elhodaky Mostafa , Jimenez Christian , Li Lin , Lang Julie , Wang Pin , Yu Min 
Published: May 2018

AbstractTriple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively. Compared to TAK1 inhibition, suppressing IL1 signaling with recombinant IL1 receptor antagonist (IL1RA) is less efficient in reducing lung metastasis, possibly due to the additional TAK1 signals coming from distinct stromal cells. Together, these observations suggest that TAK1 may play a central role in promoting TNBC cell adaptation to the lung microenvironment by facilitating positive feedback signaling mediated by P38. Approaches targeting the key TAK1-P38 signal could offer a novel means for suppressing TNBC lung metastasis.
Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection
Authors: Rycroft Julian A. , Gollan Bridget , Grabe Grzegorz J. , Hall Alexander , Cheverton Angela M. , Larrouy-Maumus Gerald , Hare Stephen A. , Helaine Sophie 
Published: May 2018

AbstractNon-typhoidal Salmonella strains are responsible for invasive infections associated with high mortality and recurrence in sub-Saharan Africa, and there is strong evidence for clonal relapse following antibiotic treatment. Persisters are non-growing bacteria that are thought to be responsible for the recalcitrance of many infections to antibiotics. Toxin–antitoxin systems are stress-responsive elements that are important for Salmonella persister formation, specifically during infection. Here, we report the analysis of persister formation of clinical invasive strains of Salmonella Typhimurium and Enteritidis in human primary macrophages. We show that all the invasive clinical isolates of both serovars that we tested produce high levels of persisters following internalization by human macrophages. Our genome comparison reveals that S. Enteritidis and S. Typhimurium strains contain three acetyltransferase toxins that we characterize structurally and functionally. We show that all induce the persister state by inhibiting translation through acetylation of aminoacyl-tRNAs. However, they differ in their potency and target partially different subsets of aminoacyl-tRNAs, potentially accounting for their non-redundant effect.
Immune system correlates of extensive limb swelling in response to conjugated pneumococcal vaccination
Authors: Recher Mike , Hirsiger Julia R. , Bigler Marc B. , Iff Martin , Lemaître Barbara , Scherer Kathrin , Häusermann Peter , Siegrist Claire-Anne , Berger Christoph T. 
Published: May 2018

AbstractPneumococcal conjugate vaccine (PCV) is recommended for adults with chronic disease. Extensive limb swelling (ELS) is an acute vigorous local inflammatory reaction following vaccination. Predisposing immune system correlates and the influence of ELS on vaccine responses are not known. Here, we report a case of a 67-year-old woman with a history of multiple pneumonias who had a detailed immunological work-up pre-vaccination because of suspected immunodeficiency. Four days following a first vaccination with PCV13 she developed ELS—mimicking erysipelas. Treatment with 20 mg cortisone completely alleviated symptoms within 2 days. Skin biopsy showed a dense dermal and subdermal infiltration dominated by CD4+ T cells and macrophages. In a multiplexed serotype-specific measurement of the anti-pneumococcal IgG response, the patient showed very broad and strong vaccine responses. Pre-vaccination titers were low for the vaccine serotypes. We did not find in vivo nor in vitro evidence of an excessive T cell response to the diphtheria-derived PCV carrier protein. However, we could demonstrate a high antibody titer to a non-vaccine serotype, indicating in vivo pre-exposure to pneumococcus bacteria. Thus, traces of pneumococcal proteins included in PCV13 may have boosted pre-existing pneumococcus-specific T helper cells, which subsequently orchestrated ELS. Our case raises awareness for the risk of vaccine-induced ELS, especially in patients with a history of recurrent pneumococcal disease and thus partial immunity.
Development of an Algorithm to Identify Patients with Physician-Documented Insomnia
Authors: Kartoun Uri , Aggarwal Rahul , Beam Andrew L. , Pai Jennifer K. , Chatterjee Arnaub K. , Fitzgerald Timothy P. , Kohane Isaac S. , Shaw Stanley Y. 
Published: May 2018

AbstractWe developed an insomnia classification algorithm by interrogating an electronic medical records (EMR) database of 314,292 patients. The patients received care at Massachusetts General Hospital (MGH), Brigham and Women’s Hospital (BWH), or both, between 1992 and 2010. Our algorithm combined structured variables (such as International Classification of Diseases 9th Revision [ICD-9] codes, prescriptions, laboratory observations) and unstructured variables (such as text mentions of sleep and psychiatric disorders in clinical narrative notes). The highest classification performance of our algorithm was achieved when it included a combination of structured variables (billing codes for insomnia, common psychiatric conditions, and joint disorders) and unstructured variables (sleep disorders and psychiatric disorders). Our algorithm had superior performance in identifying insomnia patients compared to billing codes alone (area under the receiver operating characteristic curve [AUROC] = 0.83 vs. 0.55 with 95% confidence intervals [CI] of 0.76–0.90 and 0.51–0.58, respectively). When applied to the 314,292-patient population, our algorithm classified 36,810 of the patients with insomnia, of which less than 17% had a billing code for insomnia. In conclusion, an insomnia classification algorithm that incorporates clinical notes is superior to one based solely on billing codes. Compared to traditional methods, our study demonstrates that a classification algorithm that incorporates physician notes can more accurately, comprehensively, and quickly identify large cohorts of insomnia patients.
Magneto-absorption spectra of hydrogen-like yellow exciton series in cuprous oxide: excitons in strong magnetic fields
Authors: Artyukhin Sergey , Fishman Dmitry , Faugeras Clément , Potemski Marek , Revcolevschi Alexandre , Mostovoy Maxim , Loosdrecht Paul H. M. van 
Published: May 2018

AbstractWe study the absorption spectra of the yellow excitons in Cu2O in high magnetic fields using polarization-resolved optical absorption measurements with a high frequency resolution. We show that the symmetry of the yellow exciton results in unusual selection rules for the optical absorption of polarized light and that the mixing of ortho- and para- excitons in magnetic field is important. The calculation of the energies of the yellow exciton series in strong and weak magnetic field limits suggests that a broad n = 2 line is comprized by two closely overlapping lines, gives a good fit to experimental data and allows to interpret the complex structure of excitonic levels.
Using network analysis for the prediction of treatment dropout in patients with mood and anxiety disorders: A methodological proof-of-concept study
Authors: Lutz Wolfgang , Schwartz Brian , Hofmann Stefan G. , Fisher Aaron J. , Husen Kristin , Rubel Julian A. 
Published: May 2018

AbstractThere are large health, societal, and economic costs associated with attrition from psychological services. The recently emerged, innovative statistical tool of complex network analysis was used in the present proof-of-concept study to improve the prediction of attrition. Fifty-eight patients undergoing psychological treatment for mood or anxiety disorders were assessed using Ecological Momentary Assessments four times a day for two weeks before treatment (3,248 measurements). Multilevel vector autoregressive models were employed to compute dynamic symptom networks. Intake variables and network parameters (centrality measures) were used as predictors for dropout using machine-learning algorithms. Networks for patients differed significantly between completers and dropouts. Among intake variables, initial impairment and sex predicted dropout explaining 6% of the variance. The network analysis identified four additional predictors: Expected force of being excited, outstrength of experiencing social support, betweenness of feeling nervous, and instrength of being active. The final model with the two intake and four network variables explained 32% of variance in dropout and identified 47 out of 58 patients correctly. The findings indicate that patients’ dynamic network structures may improve the prediction of dropout. When implemented in routine care, such prediction models could identify patients at risk for attrition and inform personalized treatment recommendations.
On spiking behaviour of oyster fungi Pleurotus djamor
Authors: Adamatzky Andrew 
Published: May 2018

AbstractWe recorded extra-cellular electrical potential of fruit bodies of oyster fungi Pleurotus djamor. We demonstrated that the fungi generate action potential like impulses of electrical potential. Trains of the spikes are observed. Two types of spiking activity are uncovered: high-frequency (period 2.6 min) and low-frequency (period 14 min); transitions between modes of spiking are illustrated. An electrical response of fruit bodies to short (5 sec) and long (60 sec) thermal stimulation with open flame is analysed in details. We show that non-stimulated fruit bodies of a cluster react to the thermal stimulation, with a single action-potential like spike, faster than the stimulated fruit body does.
Single measurement detection of individual cell ionic oscillations using an n-type semiconductor – electrolyte interface
Authors: Pietruszka Mariusz , Olszewska Monika , Machura Lukasz , Rówiński Edward 
Published: May 2018

AbstractPollen tubes are used as models in studies on the type of tip-growth in plants. They are an example of polarised and rapid growth because pollen tubes are able to quickly invade the flower pistil in order to accomplish fertilisation. How different ionic fluxes are perceived, processed or generated in the pollen tube is still not satisfactorily understood. In order to measure the H+, K+, Ca2+ and Cl− fluxes of a single pollen tube, we developed an Electrical Lab on a Photovoltaic-Chip (ELoPvC) on which the evolving cell was immersed in an electrolyte of a germination medium. Pollen from Hyacinthus orientalis L. was investigated ex vivo. We observed that the growing cell changed the (redox) potential in the medium in a periodic manner. This subtle measurement was feasible due to the effects that were taking place at the semiconductor-liquid interface. The experiment confirmed the existence of the ionic oscillations that accompany the periodic extension of pollen tubes, thereby providing – in a single run – the complete discrete frequency spectrum and phase relationships of the ion gradients and fluxes, while all of the metabolic and enzymatic functions of the cell life cycle were preserved. Furthermore, the global 1/fα characteristic of the power spectral density, which corresponds to the membrane channel noise, was found.