bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary vasodilator therapy in the failing Fontan circulation: rationale and efficacy
Authors: Snarr Brian S. , Paridon Stephen M. , Rychik Jack , Goldberg David J. 
Published: December 2015

AbstractThe Fontan operation is the final step of palliation for patients with a functionally single ventricle. Since its introduction in the 1970s, the Fontan surgery has become part of a successful surgical strategy that has improved single ventricle mortality. In recent years, we have become more aware of the limitations and long-term consequences of the Fontan physiology. Pulmonary vascular resistance plays an important role in total cavopulmonary circulation, and has been identified as a potential therapeutic target to mitigate Fontan sequelae. In this review, we will discuss the results of different pulmonary vasodilator trials and the use of pulmonary vasodilators as a treatment strategy for Fontan patients.
A basal-like breast cancer-specific role for SRF–IL6 in YAP-induced cancer stemness
Authors: Kim Tackhoon , Yang Suk-Jin , Hwang Daehee , Song Jinhoi , Kim Minchul , Kyum Kim Sang , Kang Keunsoo , Ahn Jaebum , Lee Daeyoup , Kim Mi-young , Kim Seyun , Seung Koo Ja , Seok Koh Sang , Kim Seon-Young , Lim Dae-Sik 
Published: December 2015

AbstractThe switch between stem/progenitor cell expansion and differentiation is critical for organ homeostasis. The mammalian Hippo pathway effector and oncoprotein YAP expands undifferentiated stem/progenitor cells in various tissues. However, the YAP-associated transcription factors and downstream targets underlying this stemness-promoting activity are poorly understood. Here we show that the SRF–IL6 axis is the critical mediator of YAP-induced stemness in mammary epithelial cells and breast cancer. Specifically, serum response factor (SRF)-mediated binding and recruitment of YAP to mammary stem cell (MaSC) signature-gene promoters induce numerous MaSC signature genes, among which the target interleukin (IL)-6 is critical for YAP-induced stemness. High SRF–YAP/TAZ expression is correlated with IL6-enriched MaSC/basal-like breast cancer (BLBC). Finally, we show that this high SRF expression enables YAP to more efficiently induce IL6 and stemness in BLBC compared with luminal-type breast cancer. Collectively, our results establish the importance of SRF–YAP–IL6 signalling in promoting MaSC-like properties in a BLBC-specific manner.
Transcriptional elongation requires DNA break-induced signalling
Authors: Bunch Heeyoun , Lawney Brian P. , Lin Yu-Fen , Asaithamby Aroumougame , Murshid Ayesha , Wang Yaoyu E. , Chen Benjamin P. C. , Calderwood Stuart K. 
Published: December 2015

AbstractWe have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28 and γH2AX on serum-induced genes and the important function of DNA-PK for Pol II pause release and transcriptional activation-coupled DDR signalling on these genes. γH2AX accumulation decreases when P-TEFb is inhibited, confirming that DDR signalling results from transcriptional elongation. In addition, transcriptional elongation-coupled DDR signalling involves topoisomerase II because inhibiting this enzyme interferes with Pol II pause release and γH2AX accumulation. Our findings propose that DDR signalling is required for effective Pol II pause release and transcriptional elongation through a novel mechanism involving TRIM28, DNA-PK and topoisomerase II.
Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression
Authors: Lomniczi Alejandro , Wright Hollis , Castellano Juan Manuel , Matagne Valerie , Toro Carlos A. , Ramaswamy Suresh , Plant Tony M. , Ojeda Sergio R. 
Published: December 2015

AbstractIn primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicatesZinc finger(ZNF) genes in timing human puberty. Here we show that hypothalamic expression of severalZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of theseZNFs,GATAD1andZNF573, also decreases in peripubertal female monkeys. However, onlyGATAD1abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery ofGATAD1orZNF573to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes,KISS1andTAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty.
Tongue Epithelium Cells from shRNA Mediated Transgenic Goat Show High Resistance to Foot and Mouth Disease Virus
Authors: Li Wenting , Wang Kejun , Kang Shimeng , Deng Shoulong , Han Hongbing , Lian Ling , Lian Zhengxing 
Published: December 2015

AbstractFoot and mouth disease induced by foot and mouth disease virus (FMDV) is severe threat to cloven-hoofed domestic animals. The gene 3Dpol in FMDV genome encodes the viral RNA polymerase, a vital element for FMDV replication. In this study, a conserved 3D-7414shRNA targeting FMDV-3Dpol gene was designed and injected into pronuclear embryos to produce the transgenic goats. Sixty-one goats were produced, of which, seven goats positively integrated 3D-7414shRNA. Loss of function assay demonstrated that siRNA effectively knockdown 3Dpol gene in skin epithelium cells of transgenic goats. Subsequently, the tongue epithelium cells from transgenic and non-transgenic goats were infected with FMDV O/YS/CHA/05 strain. A significant decrease of virus titres and virus copy number was observed in cells of transgenic goats compared with that of non-transgenic goats, which indicated that 3D-7414siRNA inhibited FMDV replication by interfering FMDV-3Dpol gene. Furthermore, we found that expression of TLR7, RIG-I and TRAF6 was lower in FMDV infected cells from transgenic goats compared to that from non-transgenic goats, which might result from lower virus copy number in transgenic goats’ cells. In conclusion, we successfully produced transgenic goats highly expressing 3D-7414siRNA targeting 3Dpol gene and the tongue epithelium cells from the transgenic goats showed effective resistance to FMDV.
Controllable Fabrication and Optical Properties of Uniform Gadolinium Oxysulfate Hollow Spheres
Authors: Chen Fashen , Chen Gen , Liu Tao , Zhang Ning , Liu Xiaohe , Luo Hongmei , Li Junhui , Chen Limiao , Ma Renzhi , Qiu Guanzhou 
Published: December 2015

AbstractUniform gadolinium oxysulfate (Gd2O2SO4) hollow spheres were successfully fabricated by calcination of corresponding Gd-organic precursor obtained via a facile hydrothermal process. The Gd2O2SO4 hollow spheres have a mean diameter of approximately 550 nm and shell thickness in the range of 30–70 nm. The sizes and morphologies of as-prepared Gd2O2SO4 hollow spheres could be deliberately controlled by adjusting the experimental parameters. Eu-doped Gd2O2SO4 hollow spheres have also been prepared for the property modification and practical applications. The structure, morphology and properties of as-prepared products were characterized by XRD, TEM, HRTEM, SEM and fluorescence spectrophotometer. Excited with ultraviolet (UV) pump laser, successful downconversion (DC) could be achieved for Eu-doped Gd2O2SO4 hollow spheres.
Rat and human STINGs profile similarly towards anticancer/antiviral compounds
Authors: Zhang Heng , Han Min-Jie , Tao Jianli , Ye Zhao-Yang , Du Xiao-Xia , Deng Ming-Jing , Zhang Xiao-Yan , Li Lan-Fen , Jiang Zheng-Fan , Su Xiao-Dong 
Published: December 2015

AbstractCyclic dinucleotides (CDNs) and antitumor/antiviral agents (DMXAA and CMA) trigger STING-dependent innate immunity activation. Accumulative evidences have showed that DMXAA and CMA selectively activate mouse, but not human STING signaling. The mechanism underlying this species selectivity remains poorly understood. In this report, we have shown that human and rat STINGs display more similar signaling profiles toward DMXAA and CMA than that of human and mouse STINGs, suggesting that rat is more suitable for preclinical testing of STING-targeted drugs. We have also determined the crystal structures of both apo rat STING and its complex with cyclic GMP-AMP with 2′5′ and 3′5′ phosphodiester linkage (2′3′-cGAMP), a human endogenous CDN. Structure-guided biochemical analysis also revealed the functional importance of the connecting loop (A140-N152) between membrane and cytosolic domains in STING activation. Taken together, these findings reveal that rat STING is more closely related to human STING in terms of substrate preference, serving as a foundation for the development of STING-targeted drugs.
Novel Iron-based ternary amorphous oxide semiconductor with very high transparency, electronic conductivity and mobility
Authors: Malasi A. , Taz H. , Farah A. , Patel M. , Lawrie B. , Pooser R. , Baddorf A. , Duscher G. , Kalyanaraman R. 
Published: December 2015

AbstractHere we report that ternary metal oxides of type (Me)2O3 with the primary metal (Me) constituent being Fe (66 atomic (at.) %) along with the two Lanthanide elements Tb (10 at.%) and Dy (24 at.%) can show excellent semiconducting transport properties. Thin films prepared by pulsed laser deposition at room temperature followed by ambient oxidation showed very high electronic conductivity (>5 × 104 S/m) and Hall mobility (>30 cm2/V-s). These films had an amorphous microstructure which was stable to at least 500 °C and large optical transparency with a direct band gap of 2.85 ± 0.14 eV. This material shows emergent semiconducting behavior with significantly higher conductivity and mobility than the constituent insulating oxides. Since these results demonstrate a new way to modify the behaviors of transition metal oxides made from unfilled d- and/or f-subshells, a new class of functional transparent conducting oxide materials could be envisioned.
Perturbation of cellular proteostasis networks identifies pathways that modulate precursor and intermediate but not mature levels of frataxin
Authors: Nabhan Joseph F. , Gooch Renea L. , Piatnitski Chekler Eugene L. , Pierce Betsy , Bulawa Christine E. 
Published: December 2015

AbstractFriedreich’s Ataxia is a genetic disease caused by expansion of an intronic trinucleotide repeat in the frataxin (FXN) gene yielding diminished FXN expression and consequently disease. Since increasing FXN protein levels is desirable to ameliorate pathology, we explored the role of major cellular proteostasis pathways and mitochondrial proteases in FXN processing and turnover. We targeted p97/VCP, the ubiquitin proteasome pathway (UPP) and autophagy with chemical inhibitors in cell lines and patient-derived cells. p97 inhibition by DBeQ increased precursor FXN levels, while UPP and autophagic flux modulators had variable effects predominantly on intermediate FXN. Our data suggest that these pathways cannot be modulated to influence mature functional FXN levels. We also targeted known mitochondrial proteases by RNA interference and discovered a novel protease PITRM1 that regulates intermediate FXN levels. Treatment with the aforementioned chemical and genetic modulators did not have a differential effect in patient cells containing lower amounts of FXN. Interestingly, a number of treatments caused a change in total amount of FXN protein, without an effect on mature FXN. Our results imply that regulation of FXN protein levels is complex and that total amounts can be modulated chemically and genetically without altering the absolute amount of mature FXN protein.
A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase
Authors: Qin Zhen , Xiao Yibei , Yang Xinbin , Mesters Jeroen R. , Yang Shaoqing , Jiang Zhengqiang 
Published: December 2015

AbstractGlycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions — a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins.
Hierarchical honeycomb auxetic metamaterials
Authors: Mousanezhad Davood , Babaee Sahab , Ebrahimi Hamid , Ghosh Ranajay , Hamouda Abdelmagid Salem , Bertoldi Katia , Vaziri Ashkan 
Published: December 2015

AbstractMost conventional materials expand in transverse directions when they are compressed uniaxially resulting in the familiar positive Poisson’s ratio. Here we develop a new class of two dimensional (2D) metamaterials with negative Poisson’s ratio that contract in transverse directions under uniaxial compressive loads leading to auxeticity. This is achieved through mechanical instabilities (i.e., buckling) introduced by structural hierarchy and retained over a wide range of applied compression. This unusual behavior is demonstrated experimentally and analyzed computationally. The work provides new insights into the role of structural organization and hierarchy in designing 2D auxetic metamaterials and new opportunities for developing energy absorbing materials, tunable membrane filters and acoustic dampeners.
Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells
Authors: Vogel Stephanie , Grabski Elena , Buschjäger Daniela , Klawonn Frank , Döring Marius , Wang Junxi , Fletcher Erika , Bechmann Ingo , Witte Torsten , Durisin Martin , Schraven Burkhart , Mangsbo Sara M. , Schönfeld Kurt , Czeloth Niklas , Kalinke Ulrich 
Published: December 2015

AbstractTreatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fcγ receptor mediated cell-cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64+ monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients’ inflamed joints that comprised enhanced numbers of CD64+ cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64+ cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64+ cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single FcγR, but also the immunological environment that is appropriate to support such interactions.
Distillation of photon entanglement using a plasmonic metamaterial
Authors: Asano Motoki , Bechu Muriel , Tame Mark , Kaya Özdemir Şahin , Ikuta Rikizo , Güney Durdu Ö. , Yamamoto Takashi , Yang Lan , Wegener Martin , Imoto Nobuyuki 
Published: December 2015

AbstractPlasmonics is a rapidly emerging platform for quantum state engineering with the potential for building ultra-compact and hybrid optoelectronic devices. Recent experiments have shown that despite the presence of decoherence and loss, photon statistics and entanglement can be preserved in single plasmonic systems. This preserving ability should carry over to plasmonic metamaterials, whose properties are the result of many individual plasmonic systems acting collectively and can be used to engineer optical states of light. Here, we report an experimental demonstration of quantum state filtering, also known as entanglement distillation, using a metamaterial. We show that the metamaterial can be used to distill highly entangled states from less entangled states. As the metamaterial can be integrated with other optical components this work opens up the intriguing possibility of incorporating plasmonic metamaterials in on-chip quantum state engineering tasks.
Nanoscale Kerr Nonlinearity Enhancement Using Spontaneously Generated Coherence in Plasmonic Nanocavity
Authors: Chen Hongyi , Ren Juanjuan , Gu Ying , Zhao Dongxing , Zhang Junxiang , Gong Qihuang 
Published: December 2015

AbstractThe enhancement of the optical nonlinear effects at nanoscale is important in the on-chip optical information processing. We theoretically propose the mechanism of the great Kerr nonlinearity enhancement by using anisotropic Purcell factors in a double-Λ type four-level system, i.e., if the bisector of the two vertical dipole moments lies in the small/large Purcell factor axis in the space, the Kerr nonlinearity will be enhanced/decreased due to the spontaneously generated coherence accordingly. Besides, when the two dipole moments are parallel, the extremely large Kerr nonlinearity increase appears, which comes from the double population trapping. Using the custom-designed resonant plasmonic nanostructure which gives an anisotropic Purcell factor environment, we demonstrate the effective nanoscale control of the Kerr nonlinearity. Such controllable Kerr nonlinearity may be realized by the state-of-the-art nanotechnics and it may have potential applications in on-chip photonic nonlinear devices.
The effects of lung and prostate cancer bone metastasis on serum osteoprotegerin levels: a meta-analysis
Authors: Zang Leyuan , Ma Min , Hu Jianxin , Qiu Hao , Huang Bo , Chu Tongwei 
Published: December 2015

AbstractBone metastasis leads to skeletal-related events in final-stage cancer patients. The incidence of prostate and lung cancers increases yearly; these cancers readily invade the bone. Some recent studies have found that serum osteoprotegerin (OPG) levels may be altered in patients with bone metastasis, whereas other reports have produced inconsistent findings. Hence, we conducted a meta-analysis to examine the effects of lung and prostate cancer on serum OPG levels. A systematic literature search was conducted using PubMed, Medline and CNKI to identify relevant studies. A total of 11 studies were included. The standardized mean difference (SMD) and 95% confidence interval (95% CI) of the bone metastasis (BM) group, the non-bone metastasis (BM-) group and healthy controls were calculated. In prostate cancer, serum OPG levels in the BM group were higher than in the BM- group and healthy controls. Additionally, no significant difference in serum OPG levels was found between the BM- group and healthy controls. In lung cancer, serum OPG levels in the BM and BM- groups were significantly increased compared with healthy controls. However, no significant difference in serum OPG levels was found between the BM and BM- groups. Studies with larger sample sizes are required to confirm these findings.
Feasibility of US-CT image fusion to identify the sources of abnormal vascularization in posterior sacroiliac joints of ankylosing spondylitis patients
Authors: Hu Zhenlong , Zhu Jiaan , Liu Fang , Wang Niansong , Xue Qin 
Published: December 2015

AbstractUltrasound (US) can be used to evaluate the inflammatory activity of the sacroiliac joints (SIJs) in ankylosing spondylitis (AS) patients, but to precisely locate the abnormal vascularization observed on color Doppler US (CDUS) was difficult. To address this issue, we performed US and computed tomography (CT) fusion imaging of SIJs with 84 inpatients and 30 controls and then assessed the sources of abnormal vascularization in the posterior SIJs of AS patients based on the fused images. Several possible factors impacting the fusion process were considered including the lesion classes of SIJ, the skinfold thickness of the sacral region and the cross-sectional levels of the first, second and third posterior sacral foramina. Our data showed high image fusion success rates at the 3 levels in the AS group (97.0%, 87.5% and 79.8%, respectively) and the control group (96.7%, 86.7% and 86.7%, respectively).The skinfold thickness was identified as the main factor affecting the success rates. The successfully fused images revealed significant differences in the distribution of abnormal vascularization between 3 levels, as detected via CDUS (P = 0.011), which suggested that inflammation occurred in distinct tissues at different levels of the SIJ (intraligamentous inflammation in Regions 1 and 2; intracapsular inflammation in Region 3).
Subsite-specific contributions of different aromatic residues in the active site architecture of glycoside hydrolase family 12
Authors: Zhang Xiaomei , Wang Shuai , Wu Xiuyun , Liu Shijia , Li Dandan , Xu Hao , Gao Peiji , Chen Guanjun , Wang Lushan 
Published: December 2015

AbstractThe active site architecture of glycoside hydrolase (GH) is a contiguous subregion of the enzyme constituted by residues clustered in the three-dimensional space, recognizing the monomeric unit of ligand through hydrogen bonds and hydrophobic interactions. Mutations of the key residues in the active site architecture of the GH12 family exerted different impacts on catalytic efficiency. Binding affinities between the aromatic amino acids and carbohydrate rings were quantitatively determined by isothermal titration calorimetry (ITC) and the quantum mechanical (QM) method, showing that the binding capacity order of Tyr>Trp>His (and Phe) was determined by their side-chain properties. The results also revealed that the binding constant of a certain residue remained unchanged when altering its location, while the catalytic efficiency changed dramatically. Increased binding affinity at a relatively distant subsite, such as the mutant of W7Y at the −4 subsite, resulted in a marked increase in the intermediate product of cellotetraose and enhanced the reactivity of endoglucanase by 144%; while tighter binding near the catalytic center, i.e. W22Y at the −2 subsite, enabled the enzyme to bind and hydrolyze smaller oligosaccharides. Clarification of the specific roles of the aromatics at different subsites may pave the way for a more rational design of GHs.