bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redesigning metabolism based on orthogonality principles
Authors: Pandit Aditya Vikram , Srinivasan Shyam , Mahadevan Radhakrishnan 
Published: May 2017

AbstractModifications made during metabolic engineering for overproduction of chemicals have network-wide effects on cellular function due to ubiquitous metabolic interactions. These interactions, that make metabolic network structures robust and optimized for cell growth, act to constrain the capability of the cell factory. To overcome these challenges, we explore the idea of an orthogonal network structure that is designed to operate with minimal interaction between chemical production pathways and the components of the network that produce biomass. We show that this orthogonal pathway design approach has significant advantages over contemporary growth-coupled approaches using a case study on succinate production. We find that natural pathways, fundamentally linked to biomass synthesis, are less orthogonal in comparison to synthetic pathways. We suggest that the use of such orthogonal pathways can be highly amenable for dynamic control of metabolism and have other implications for metabolic engineering.
Recent enhancement of central Pacific El Niño variability relative to last eight centuries
Authors: Liu Yu , Cobb Kim M. , Song Huiming , Li Qiang , Li Ching-Yao , Nakatsuka Takeshi , An Zhisheng , Zhou Weijian , Cai Qiufang , Li Jinbao , Leavitt Steven W. , Sun Changfeng , Mei Ruochen , Shen Chuan-Chou , Chan Ming-Hsun , Sun Junyan , Yan Libin , Lei Ying , Ma Yongyong , Li Xuxiang , Chen Deliang , Linderholm Hans W. 
Published: May 2017

AbstractThe far-reaching impacts of central Pacific El Niño events on global climate differ appreciably from those associated with eastern Pacific El Niño events. Central Pacific El Niño events may become more frequent in coming decades as atmospheric greenhouse gas concentrations rise, but the instrumental record of central Pacific sea-surface temperatures is too short to detect potential trends. Here we present an annually resolved reconstruction of NIÑO4 sea-surface temperature, located in the central equatorial Pacific, based on oxygen isotopic time series from Taiwan tree cellulose that span from 1190 AD to 2007 AD. Our reconstruction indicates that relatively warm Niño4 sea-surface temperature values over the late twentieth century are accompanied by higher levels of interannual variability than observed in other intervals of the 818-year-long reconstruction. Our results imply that anthropogenic greenhouse forcing may be driving an increase in central Pacific El Niño-Southern Oscillation variability and/or its hydrological impacts, consistent with recent modelling studies.
TGF-β activation by bone marrow-derived thrombospondin-1 causes Schistosoma- and hypoxia-induced pulmonary hypertension
Authors: Kumar Rahul , Mickael Claudia , Kassa Biruk , Gebreab Liya , Robinson Jeffrey C. , Koyanagi Daniel E. , Sanders Linda , Barthel Lea , Meadows Christina , Fox Daniel , Irwin David , Li Min , McKeon B. Alexandre , Riddle Suzette , Dale Brown R. , Morgan Leslie E. , Evans Christopher M. , Hernandez-Saavedra Daniel , Bandeira Angela , Maloney James P. , Bull Todd M. , Janssen William J. , Stenmark Kurt R. , Tuder Rubin M. , Graham Brian B. 
Published: May 2017

AbstractPulmonary arterial hypertension (PAH) is an obstructive disease of the precapillary pulmonary arteries. Schistosomiasis-associated PAH shares altered vascular TGF-β signalling with idiopathic, heritable and autoimmune-associated etiologies; moreover, TGF-β blockade can prevent experimental pulmonary hypertension (PH) in pre-clinical models. TGF-β is regulated at the level of activation, but how TGF-β is activated in this disease is unknown. Here we show TGF-β activation by thrombospondin-1 (TSP-1) is both required and sufficient for the development of PH inSchistosoma-exposed mice. FollowingSchistosomaexposure, TSP-1 levels in the lung increase, via recruitment of circulating monocytes, while TSP-1 inhibition or knockout bone marrow prevents TGF-β activation and protects against PH development. TSP-1 blockade also prevents the PH in a second model, chronic hypoxia. Lastly, the plasma concentration of TSP-1 is significantly increased in subjects with scleroderma following PAH development. Targeting TSP-1-dependent activation of TGF-β could thus be a therapeutic approach in TGF-β-dependent vascular diseases.
Clonally stable Vκ allelic choice instructs Igκ repertoire
Authors: Levin-Klein Rena , Fraenkel Shira , Lichtenstein Michal , Matheson Louise S. , Bartok Osnat , Nevo Yuval , Kadener Sebastian , Corcoran Anne E. , Cedar Howard , Bergman Yehudit 
Published: May 2017

AbstractAlthough much has been done to understand how rearrangement of the Igκ locus is regulated during B-cell development, little is known about the way the variable (V) segments themselves are selected. Here we show, using B6/Cast hybrid pre-B-cell clones, that a limited number of V segments on each allele is stochastically activated as characterized by the appearance of non-coding RNA and histone modifications. The activation states are clonally distinct, stable across cell division and developmentally important in directing the Ig repertoire upon differentiation. Using a new approach of allelic ATAC-seq, we demonstrate that the Igκ V alleles have differential chromatin accessibility, which may serve as the underlying basis of clonal maintenance at this locus, as well as other instances of monoallelic expression throughout the genome. These findings highlight a new level of immune system regulation that optimizes gene diversity.
Glucose represses dendritic cell-induced T cell responses
Authors: Lawless Simon J. , Kedia-Mehta Nidhi , Walls Jessica F. , McGarrigle Ryan , Convery Orla , Sinclair Linda V. , Navarro Maria N. , Murray James , Finlay David K. 
Published: May 2017

AbstractGlucose and glycolysis are important for the proinflammatory functions of many immune cells, and depletion of glucose in pathological microenvironments is associated with defective immune responses. Here we show a contrasting function for glucose in dendritic cells (DCs), as glucose represses the proinflammatory output of LPS-stimulated DCs and inhibits DC-induced T-cell responses. A glucose-sensitive signal transduction circuit involving the mTOR complex 1 (mTORC1), HIF1α and inducible nitric oxide synthase (iNOS) coordinates DC metabolism and function to limit DC-stimulated T-cell responses. When multiple T cells interact with a DC, they compete for nutrients, which can limit glucose availability to the DCs. In such DCs, glucose-dependent signalling is inhibited, altering DC outputs and enhancing T-cell responses. These data reveal a mechanism by which T cells regulate the DC microenvironment to control DC-induced T-cell responses and indicate that glucose is an important signal for shaping immune responses.
Attosecond interferometry with self-amplified spontaneous emission of a free-electron laser
Authors: Usenko Sergey , Przystawik Andreas , Jakob Markus Alexander , Lazzarino Leslie Lamberto , Brenner Günter , Toleikis Sven , Haunhorst Christian , Kip Detlef , Laarmann Tim 
Published: May 2017

AbstractLight-phase-sensitive techniques, such as coherent multidimensional spectroscopy, are well-established in a broad spectral range, already spanning from radio-frequencies in nuclear magnetic resonance spectroscopy to visible and ultraviolet wavelengths in nonlinear optics with table-top lasers. In these cases, the ability to tailor the phases of electromagnetic waves with high precision is essential. Here we achieve phase control of extreme-ultraviolet pulses from a free-electron laser (FEL) on the attosecond timescale in a Michelson-type all-reflective interferometric autocorrelator. By varying the relative phase of the generated pulse replicas with sub-cycle precision we observe the field interference, that is, the light-wave oscillation with a period of 129 as. The successful transfer of a powerful optical method towards short-wavelength FEL science and technology paves the way towards utilization of advanced nonlinear methodologies even at partially coherent soft X-ray FEL sources that rely on self-amplified spontaneous emission.
Persistent LHPA Activation in German Individuals Raised in an Overprotective Parental Behavior
Authors: Ullmann E. , Licinio J. , Barthel A. , Petrowski K. , Stalder T. , Bornstein S. R. , Kirschbaum C. 
Published: May 2017

AbstractParental upbringing may affect their offspring’s mental state across the entire lifespan. Overprotective parental child-rearing style may increase the disease burden in the offspring. Furthermore, this child-rearing style may also play a pathogenetic role by transmitting trauma- and stressor-related disorders (TSRD) across generations. Studies with animals have demonstrated that the mother’s immediate and expansive protection of the newborn decreases the limbic-hypothalamic-pituitary-adrenal (LHPA) axis activity in the offspring. However, few studies have investigated how stress impact humans raised in an overprotective manner. In a cross-sectional study with 40 healthy students recalling their overprotective upbringing, we show an increase in the dehydroepiandrostendione (DHEA) concentration and a reduction in the cortisol/DHEA-ratio in hair. Additionally, this child rearing style was associated with heightened indications of mental burden, depressiveness, and sense of coherence. Our results provide insight into the roots and consequences of psychological trauma across several generations. Further investigations focusing particularly on multigenerational transmission in extremely burdened families will augment our results.
Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice
Authors: Colaianni Graziana , Mongelli Teresa , Cuscito Concetta , Pignataro Paolo , Lippo Luciana , Spiro Giovanna , Notarnicola Angela , Severi Ilenia , Passeri Giovanni , Mori Giorgio , Brunetti Giacomina , Moretti Biagio , Tarantino Umberto , Colucci Silvia C. , Reseland Janne E. , Vettor Roberto , Cinti Saverio , Grano Maria 
Published: May 2017

AbstractWe previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass. Here we report that treatment with recombinant Irisin prevented bone loss in hind-limb suspended mice when administered during suspension (preventive protocol) and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks (curative protocol). MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented a dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin protected against muscle mass decline in the hind-limb suspended mice, and maintained the fiber cross-sectional area. Notably, the decrease of myosin type II expression in unloaded mice was completely prevented by r-Irisin administration. Our data reveal for the first time that Irisin retrieves disuse‐induced bone loss and muscle atrophy. These findings may lead to development of an Irisin-based therapy for elderly immobile osteoporotic and physically disable patients, and might represent a countermeasure for astronauts subjected to microgravity-induced bone and muscle losses.
Melon13-lipoxygenase CmLOX18 may be involved in C6 volatiles biosynthesis in fruit
Authors: Zhang Chong , Cao Songxiao , Jin Yazhong , Ju Lijun , Chen Qiang , Xing Qiaojuan , Qi Hongyan 
Published: May 2017

AbstractTo better understand the function role of the melon CmLOX18 gene in the biosynthesis of C6 volatiles during fruit ripening, we biochemically characterized CmLOX18 and identified its subcellular localization in transgenic tomato plants. Heterologous expression in yeast cells showed that the molecular weight of the CmLOX18 protein was identical to that predicted, and that this enzyme possesseed lipoxygenase activity. Linoleic acid was demonstrated to be the preferred substrate for the purified recombinant CmLOX18 protein, which exhibited optimal catalytic activity at pH 4.5 and 30 °C. Chromatogram analysis of the reaction product indicated that the CmLOX18 protein exhibited positional specificity, as evidenced by its release of only a C-13 oxidized product. Subcellular localization analysis by transient expression in Arabidopsis protoplasts showed that CmLOX18 was localized to non-chloroplast organelles. When the CmLOX18 gene was transgenically expressed in tomato via Agrobacterium tumefaciens-mediated transformation, it was shown to enhance expression levels of the tomato hydroperoxide lyase gene LeHPL, whereas the expression levels of six TomLox genes were little changed. Furthermore, transgenic tomato fruits exhibited increases in the content of the C6 volatiles, namely hexanal, (Z)-3-hexanal, and (Z)-3-hexen-1-ol, indicating that CmLOX18 probably plays an important role in the synthesis of C6 compounds in fruits.
Genome-wide profiling and differential expression of microRNA in rat pluripotent stem cells
Authors: Sherstyuk Vladimir V. , Medvedev Sergey P. , Elisaphenko Evgeniy A. , Vaskova Evgeniya A. , Ri Maxim T. , Vyatkin Yuri V. , Saik Olga V. , Shtokalo Dmitry N. , Pokushalov Evgeniy A. , Zakian Suren M. 
Published: May 2017

AbstractMicroRNAs (miRNAs) constitute a class of small noncoding RNAs that plays an important role in the post-transcriptional regulation of gene expression. Much evidence has demonstrated that miRNAs are involved in regulating the human and mouse pluripotency. Nevertheless, to our knowledge, miRNAs in the pluripotent stem cells of one of the most commonly used model organisms – the Rattus norvegicus have not been studied. In the present study, we performed deep sequencing of small RNA molecules in the embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells of laboratory rats. Bioinformatics analysis revealed 674 known miRNAs and 394 novel miRNA candidates in all of the samples. Expression of known pluripotency-associated miRNAs, such as the miR-290–295 and miR-183-96-182 clusters as well as members of the miR-200 family, was detected in rat pluripotent stem cells. Analysis of the targets of differentially expressed known and novel miRNAs showed their involvement in the regulation of pluripotency and the reprogramming process in rats. Bioinformatics and systems biology approaches identified potential pathways that are regulated by these miRNAs. This study contributes to our understanding of miRNAs in the regulation of pluripotency and cell reprogramming in the laboratory rat.
Pulmonary emphysema is a risk factor for radiation pneumonitis in NSCLC patients with squamous cell carcinoma after thoracic radiation therapy
Authors: Zhou Ziyang , Song Xiao , Wu Ailu , Liu Hui , Wu Hongyu , Wu Qiongya , Liu Yu , Li Yefei , Cai Yong , Liang Shixiong 
Published: May 2017

AbstractPulmonary emphysema (PE) has been demonstrated to have a high prevalence in patients with locally advanced non-small cell lung cancer (NSCLC). A total of 153 patients with locally advanced NSCLC were enrolled in this study to investigate the association between PE and radiation pneumonitis (RP) after definitive thoracic radiation therapy (TRT). The incidence of RP in Grade 2, 3 and 5 were 11.1%, 9.8% and 0.7%, respectively. Univariate analysis revealed that age, PE, forced vital capacity (FVC), arterial partial pressure of oxygen (PO2) and mean lung dose (MLD) were significantly associated with the risk of Grade ≥2 or Grade ≥3 RP in patients with squamous cell carcinoma (SCC, P < 0.05). Logistic analysis demonstrated that PE was an independent risk factor of RP in SCC (P < 0.05). Receiver operating characteristics (ROC) analysis revealed that the combination of age, PE, FVC, PO2 and MLD had a higher value to predict RP in SCC (AUC = 0.856 in Grade ≥2 RP and 0.882 in Grade ≥3 RP, respectively). Kaplan-Meier analysis revealed that the more severe the PE, the higher the incidence of RP in SCC. Our results revealed that PE was a high risk factor for locally advanced NSCLC patients followed definitive TRT, especially for SCC patients.
Magnetic character of holmium atom adsorbed on platinum surface
Authors: Shick A. B. , Shapiro D. S. , Kolorenc J. , Lichtenstein A. I. 
Published: May 2017

AbstractWe address a recent controversy concerning the magnetic state of holmium adatom on platinum surface. Within a combination of the density functional theory (DFT) with the exact diagonalization (ED) of Anderson impurity model, the 〈J
z
〉 = 0 paramagnetic ground state |J = 8, J
z
= ±8〉 is found. In an external magnetic field, this state is transformed to a spin-polarized state with 〈J
z
〉 ≈ 6.7. We emphasize the role of 5d–4f interorbital exchange polarization in modification of the 4f shell energy spectrum.
Arsenic mobilization in shallow aquifers due to CO2 and brine intrusion from storage reservoirs
Authors: Xiao Ting , Dai Zhenxue , Viswanathan Hari , Hakala Alexandra , Cather Martha , Jia Wei , Zhang Yongchao , McPherson Brian 
Published: May 2017

AbstractWe developed an integrated framework of combined batch experiments and reactive transport simulations to quantify water-rock-CO2 interactions and arsenic (As) mobilization responses to CO2 and/or saline water leakage into USDWs. Experimental and simulation results suggest that when CO2 is introduced, pH drops immediately that initiates release of As from clay minerals. Calcite dissolution can increase pH slightly and cause As re-adsorption. Thus, the mineralogy of the USDW is ultimately a determining factor of arsenic fate and transport. Salient results suggest that: (1) As desorption/adsorption from/onto clay minerals is the major reaction controlling its mobilization, and clay minerals could mitigate As mobilization with surface complexation reactions; (2) dissolution of available calcite plays a critical role in buffering pH; (3) high salinity in general hinders As release from minerals; and (4) the magnitude and quantitative uncertainty of As mobilization are predicated on the values of reaction rates and surface area of calcite, adsorption surface areas and equilibrium constants of clay minerals, and cation exchange capacity. Results of this study are intended to improve ability to quantify risks associated with potential leakage of reservoir fluids into shallow aquifers, in particular the possible environmental impacts of As mobilization at carbon sequestration sites.
Novel rapid-immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer
Authors: Terata Kaori , Saito Hajime , Nanjo Hiroshi , Hiroshima Yuko , Ito Satoru , Narita Kasumi , Akagami Yoichi , Nakamura Ryuta , Konno Hayato , Ito Aki , Motoyama Satoru , Minamiya Yoshihiro 
Published: May 2017

AbstractAxillary lymph node status and pathological diagnosis of sentinel lymph nodes (SLNs) is a prognostic factor that influences management of postoperative therapy. Recent reports indicate that one-step nucleic acid amplification and hematoxylin and eosin (HE)-stained frozen sections are effective for intraoperative diagnosis of SLNs. In the present study, we report a rapid-immunohistochemical staining (R-IHC) method that enables intraoperative detection of SLN metastases within 16 min using an anti-cytokeratin antibody. This is the first report on SLN diagnosis using R-IHC in patients with breast cancer. We prospectively examined 160 dissected SLNs from 108 breast cancer patients who underwent surgery at our institute. The dissected SLNs were sectioned and conventionally stained with HE or immunohistochemically labeled with anti-cytokeratin antibody using R-IHC procedures. Intraoperative R-IHC analyses were completed within 16 min, after which diagnoses were made by two pathologists. The total time required for intraoperative diagnosis was about 20 min. In this study series, R-IHC detected four metastatic SLNs that were undetected using conventional HE staining (4/20, 20.0%). Compared with subsequent permanent diagnosis, R-IHC offered 95.2% sensitivity and 100% specificity. These findings indicate R-IHC is a clinically applicable technique that enables precise and quick intraoperative detection of micro- and macrometastasis in breast cancer.
Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
Authors: Liu Xuemei , Wu Zhixiang , Lian Jiamei , Hu Chang-Hua , Huang Xu-Feng , Deng Chao 
Published: May 2017

AbstractChronic treatment with second-generation antipsychotic drugs (SGAs) has been associated with an increased risk of metabolic syndrome. To evaluate the longitudinal changes in glucose-lipid homeostasis after SGA use, we studied the time-dependent effects of olanzapine (OLZ) (3 mg/kg, b.i.d.) or clozapine (CLZ) (20 mg/kg, b.i.d.) treatment on metabolic profiles for 9 weeks in rats. Although only OLZ significantly increased body weight in rats, both OLZ and CLZ elevated blood lipid levels. Chronic OLZ treatment induced significant weight gain leading to a higher fasting insulin level and impaired glucose tolerance, whereas CLZ lowered fasting insulin levels and impaired glucose tolerance independent of weight gain. Treatment with both drugs deranged AKT/GSK phosphorylation and up-regulated muscarinic M3 receptors in the rats’ livers. Consistent with an elevation in lipid levels, both OLZ and CLZ significantly increased the protein levels of nuclear sterol regulatory element-binding proteins (SREBPs) in the liver, which was associated with improvement in hepatic histamine H1R. However, enhanced carbohydrate response element binding protein (ChREBP) signalling was observed in only CLZ-treated rats. These results suggest that SGA-induced glucose-lipid metabolic disturbances could be independent of weight gain, possibly through activation of SREBP/ChREBP in the liver.
E. coli promotes human Vγ9Vδ2 T cell transition from cytokine-producing bactericidal effectors to professional phagocytic killers in a TCR-dependent manner
Authors: Barisa M. , Kramer A. M. , Majani Y. , Moulding D. , Saraiva L. , Bajaj-Elliott M. , Anderson J. , Gustafsson K. 
Published: May 2017

AbstractγδT cells provide immune-surveillance and host defense against infection and cancer. Surprisingly, functional details of γδT cell antimicrobial immunity to infection remain largely unexplored. Limited data suggests that γδT cells can phagocytose particles and act as professional antigen-presenting cells (pAPC). These potential functions, however, remain controversial. To better understand γδT cell-bacterial interactions, anex vivoco-culture model of human peripheral blood mononuclear cell (PBMC) responses toEscherichia coliwas employed. Vγ9Vδ2 cells underwent rapid T cell receptor (TCR)-dependent proliferation and functional transition from cytotoxic, inflammatory cytokine immunity, to cell expansion with diminished cytokine but increased costimulatory molecule expression, and capacity for professional phagocytosis. Phagocytosis was augmented by IgG opsonization, and inhibited by TCR-blockade, suggesting a licensing interaction involving the TCR and FcγR. Vγ9Vδ2 cells displayed potent cytotoxicity through TCR-dependent and independent mechanisms. We conclude that γδT cells transition from early inflammatory cytotoxic killers to myeloid-like APC in response to infectious stimuli.