bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased tumor-infiltrating CD45RA−CCR7− regulatory T-cell subset with immunosuppressive properties foster gastric cancer progress
Authors: Mao Fang-yuan , Kong Hui , Zhao Yong-liang , Peng Liu-sheng , Chen Weisan , Zhang Jin-yu , Cheng Ping , Wang Ting-ting , Lv Yi-pin , Teng Yong-sheng , Fu Xiao-long , Liu Yu-gang , Wu Xiao-long , Hao Chuan-jie , You Nan , Luo Ping , Yu Pei-wu , Zou Quan-ming , Guo Gang , Zhuang Yuan 
Published: August 2017

AbstractRegulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA−CCR7− Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA−CCR7− Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR. Gastric tumor-derived TNF-α induced CD45RA−CCR7− Treg subset with similar phenotype to their status in tumors and inhibited their HLA-DR expression via activating STAT3 phosphorylation. These tumor-associated CD45RA−CCR7− Treg subset exerted superior immunosuppressive properties to effectively suppress CD8+ T cells’ anti-tumor function including CD8+ T-cell IFN-γ and granzyme B (GrB) production as well as CD8+ T-cell proliferation in vitro, and also contributed to the growth and progression of human gastric tumors in vivo, via IL-10 secretion and cell–cell contact mechanisms. Moreover, increased tumor-infiltrating CD45RA−CCR7− Treg subset as well as higher intratumoral CD45RA−CCR7− Treg/CD8+ T-cell ratio was associated with advanced disease progression and reduced GC patient survival. This study therefore identifies a novel immunosuppressive pathway involving CD45RA−CCR7− Treg subset development within the GC microenvironment. Efforts to inhibit this pathway may therefore prove a valuable strategy to prevent, and to treat this immune suppressive of GC.
Identification of an insect-produced olfactory cue that primes plant defenses
Authors: Helms Anjel M. , De Moraes Consuelo M. , Tröger Armin , Alborn Hans T. , Francke Wittko , Tooker John F. , Mescher Mark C. 
Published: August 2017

AbstractIt is increasingly clear that plants perceive and respond to olfactory cues. Yet, knowledge about the specificity and sensitivity of such perception remains limited. We previously documented priming of anti-herbivore defenses in tall goldenrod plants (Solidago altissima) by volatile emissions from a specialist herbivore, the goldenrod gall fly (Eurosta solidaginis). Here, we explore the specific chemical cues mediating this interaction. We report that E,S-conophthorin, the most abundant component of the emission of male flies, elicits a priming response equivalent to that observed for the overall blend. Furthermore, while the strength of priming is dose dependent, plants respond even to very low concentrations of E,S-conophthorin relative to typical fly emissions. Evaluation of other blend components yields results consistent with the hypothesis that priming in this interaction is mediated by a single compound. These findings provide insights into the perceptual capabilities underlying plant defense priming in response to olfactory cues.
Biochemical phosphates observed using hyperpolarized 31P in physiological aqueous solutions
Authors: Nardi-Schreiber Atara , Gamliel Ayelet , Harris Talia , Sapir Gal , Sosna Jacob , Gomori J. Moshe , Katz-Brull Rachel 
Published: August 2017

AbstractThe dissolution-dynamic nuclear polarization technology had previously enabled nuclear magnetic resonance detection of various nuclei in a hyperpolarized state. Here, we show the hyperpolarization of 31P nuclei in important biological phosphates (inorganic phosphate and phosphocreatine) in aqueous solutions. The hyperpolarized inorganic phosphate showed an enhancement factor >11,000 (at 5.8 T, 9.3% polarization) in D2O (T1 29.4 s). Deuteration and the solution composition and pH all affected the lifetime of the hyperpolarized state. This capability opens up avenues for real-time monitoring of phosphate metabolism, distribution, and pH sensing in the live body without ionizing radiation. Immediate changes in the microenvironment pH have been detected here in a cell-free system via the chemical shift of hyperpolarized inorganic phosphate. Because the 31P nucleus is 100% naturally abundant, future studies on hyperpolarized phosphates will not require expensive isotope labeling as is usually required for hyperpolarization of other substrates.
Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation
Authors: Tan Hayden Weng Siong , Sim Arthur Yi Loong , Long Yun Chau 
Published: August 2017

AbstractActivation of autophagy and elevation of glutamine synthesis represent key adaptations to maintain amino acid balance during starvation. In this study, we investigate the role of autophagy and glutamine on the regulation of mTORC1, a critical kinase that regulates cell growth and proliferation. We report that supplementation of glutamine alone is sufficient to restore mTORC1 activity during prolonged amino acid starvation. Inhibition of autophagy abolishes the restorative effect of glutamine, suggesting that reactivation of mTORC1 is autophagy-dependent. Inhibition of glutaminolysis or transamination impairs glutamine-mediated mTORC1 reactivation, suggesting glutamine reactivates mTORC1 specifically through its conversion to glutamate and restoration of non-essential amino acid pool. Despite a persistent drop in essential amino acid pool during amino acid starvation, crosstalk between glutamine and autophagy is sufficient to restore insulin sensitivity of mTORC1. Thus, glutamine metabolism and autophagy constitute a specific metabolic program which restores mTORC1 activity during amino acid starvation.
Multi-orbital charge transfer at highly oriented organic/metal interfaces
Authors: Zamborlini Giovanni , Lüftner Daniel , Feng Zhijing , Kollmann Bernd , Puschnig Peter , Dri Carlo , Panighel Mirko , Di Santo Giovanni , Goldoni Andrea , Comelli Giovanni , Jugovac Matteo , Feyer Vitaliy , Schneider Claus Michael 
Published: August 2017

AbstractThe molecule–substrate interaction plays a key role in charge injection organic-based devices. Charge transfer at molecule–metal interfaces strongly affects the overall physical and magnetic properties of the system, and ultimately the device performance. Here, we report theoretical and experimental evidence of a pronounced charge transfer involving nickel tetraphenyl porphyrin molecules adsorbed on Cu(100). The exceptional charge transfer leads to filling of the higher unoccupied orbitals up to LUMO+3. As a consequence of this strong interaction with the substrate, the porphyrin’s macrocycle sits very close to the surface, forcing the phenyl ligands to bend upwards. Due to this adsorption configuration, scanning tunneling microscopy cannot reliably probe the states related to the macrocycle. We demonstrate that photoemission tomography can instead access the Ni-TPP macrocycle electronic states and determine the reordering and filling of the LUMOs upon adsorption, thereby confirming the remarkable charge transfer predicted by density functional theory calculations.
Maximum entropy models capture melodic styles
Authors: Sakellariou Jason , Tria Francesca , Loreto Vittorio , Pachet Francois 
Published: August 2017

AbstractWe introduce a Maximum Entropy model able to capture the statistics of melodies in music. The model can be used to generate new melodies that emulate the style of a given musical corpus. Instead of using the n–body interactions of (n−1)–order Markov models, traditionally used in automatic music generation, we use a k-nearest neighbour model with pairwise interactions only. In that way, we keep the number of parameters low and avoid over-fitting problems typical of Markov models. We show that long-range musical phrases don’t need to be explicitly enforced using high-order Markov interactions, but can instead emerge from multiple, competing, pairwise interactions. We validate our Maximum Entropy model by contrasting how much the generated sequences capture the style of the original corpus without plagiarizing it. To this end we use a data-compression approach to discriminate the levels of borrowing and innovation featured by the artificial sequences. Our modelling scheme outperforms both fixed-order and variable-order Markov models. This shows that, despite being based only on pairwise interactions, our scheme opens the possibility to generate musically sensible alterations of the original phrases, providing a way to generate innovation.
A multidimensional phasor approach reveals LAURDAN photophysics in NIH-3T3 cell membranes
Authors: Malacrida Leonel , Jameson David M. , Gratton Enrico 
Published: August 2017

AbstractMammalian cell membranes have different phospholipid composition and cholesterol content, displaying a profile of fluidity that depends on their intracellular location. Among the dyes used in membrane studies, LAURDAN has the advantage to be sensitive to the lipid composition as well as to membrane fluidity. The LAURDAN spectrum is sensitive to the lipid composition and dipolar relaxation arising from water penetration, but disentangling lipid composition from membrane fluidity can be obtained if time resolved spectra could be measured at each cell location. Here we describe a method in which spectral and lifetime information obtained in different measurements at the same plane in a cell are used in the phasor plot providing a solution to analyze multiple lifetime or spectral data through a common visualization approach. We exploit a property of phasor plots based on the reciprocal role of the phasor plot and the image. In the phasor analysis each pixel of the image is associated with a phasor and each phasor maps to pixels and features in the image. In this paper the lifetime and spectral fluorescence data are used simultaneously to determine the contribution of polarity and dipolar relaxations of LAURDAN in each pixel of an image.
Soy Improves Cardiometabolic Health and Cecal Microbiota in Female Low-Fit Rats
Authors: Cross Tzu-Wen L. , Zidon Terese M. , Welly Rebecca J. , Park Young-Min , Britton Steven L. , Koch Lauren G. , Rottinghaus George E. , de Godoy Maria R. Cattai , Padilla Jaume , Swanson Kelly S. , Vieira-Potter Victoria J. 
Published: August 2017

AbstractPhytoestrogen-rich soy is known to ameliorate menopause-associated obesity and metabolic dysfunction for reasons that are unclear. The gut microbiota have been linked with the development of obesity and metabolic dysfunction. We aimed to determine the impact of soy on cardiometabolic health, adipose tissue inflammation, and the cecal microbiota in ovariectomized (OVX) rats bred for low-running capacity (LCR), a model that has been previously shown to mimic human menopause compared to sham-operated (SHM) intact control LCR rats. In this study, soy consumption, without affecting energy intake or physical activity, significantly improved insulin sensitivity and body composition of OVX rats bred for low-running capacity. Furthermore, soy significantly improved blood lipid profile, adipose tissue inflammation, and aortic stiffness of LCR rats. Compared to a soy-free control diet, soy significantly shifted the cecal microbial community of LCR rats, resulting in a lower Firmicutes:Bacteroidetes ratio. Correlations among metabolic parameters and cecal bacterial taxa identified in this study suggest that taxa Prevotella, Dorea, and Phascolarctobacterium may be taxa of interest. Our results suggest that dietary soy ameliorates adiposity, insulin sensitivity, adipose tissue inflammation, and arterial stiffness and exerts a beneficial shift in gut microbial communities in a rat model that mimics human menopause.
Simulation of Subject-Specific Progression of Knee Osteoarthritis and Comparison to Experimental Follow-up Data: Data from the Osteoarthritis Initiative
Authors: Liukkonen Mimmi K. , Mononen Mika E. , Klets Olesya , Arokoski Jari P. , Saarakkala Simo , Korhonen Rami K. 
Published: August 2017

AbstractEconomic costs of osteoarthritis (OA) are considerable. However, there are no clinical tools to predict the progression of OA or guide patients to a correct treatment for preventing OA. We tested the ability of our cartilage degeneration algorithm to predict the subject-specific development of OA and separate groups with different OA levels. The algorithm was able to predict OA progression similarly with the experimental follow-up data and separate subjects with radiographical OA (Kellgren-Lawrence (KL) grade 2 and 3) from healthy subjects (KL0). Maximum degeneration and degenerated volumes within cartilage were significantly higher (p < 0.05) in OA compared to healthy subjects, KL3 group showing the highest degeneration values. Presented algorithm shows a great potential to predict subject-specific progression of knee OA and has a clinical potential by simulating the effect of interventions on the progression of OA, thus helping decision making in an attempt to delay or prevent further OA symptoms.
Nevirapine induced mitochondrial dysfunction in HepG2 cells
Authors: Paemanee Atchara , Sornjai Wannapa , Kittisenachai Suthathip , Sirinonthanawech Naraporn , Roytrakul Sittiruk , Wongtrakul Jeerang , Smith Duncan R. 
Published: August 2017

AbstractNevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor frequently used in combination with other antiretroviral agents for highly active antiretroviral therapy (HAART) of patients infected with the human immunodeficiency virus type 1 (HIV-1). However NVP can cause serious, life-threatening complications. Hepatotoxicity is one of the most severe adverse effects, particularly in HIV patients with chronic hepatitis C virus co-infection as these patients can develop liver toxicity after a relatively short course of treatment. However, the mechanism of NVP-associated hepatotoxicity remains unclear. This study sought to investigate the effect of NVP on protein expression in liver cells using a proteomic approach. HepG2 cells were treated or not treated with NVP and proteins were subsequently resolved by two-dimensional gel electrophoresis. A total of 33 differentially regulated proteins were identified, of which nearly 40% (13/33) were mitochondrial proteins. While no obvious differences were observed between NVP treated and untreated cells after staining mitochondria with mitotracker, RT-PCR expression analysis of three mitochondrially encoded genes showed all were significantly up-regulated in NVP treated cells. Mitochondrial dysfunction was observed in response to treatment even with slightly sub-optimal therapeutic treatment concentrations of NVP. This study shows that NVP induces mitochondrial dysregulation in HepG2 cells.
Logic programming reveals alteration of key transcription factors in multiple myeloma
Authors: Miannay Bertrand , Minvielle Stéphane , Roux Olivier , Drouin Pierre , Avet-Loiseau Hervé , Guérin-Charbonnel Catherine , Gouraud Wilfried , Attal Michel , Facon Thierry , Munshi Nikhil C , Moreau Philippe , Campion Loïc , Magrangeas Florence , Guziolowski Carito 
Published: August 2017

AbstractInnovative approaches combining regulatory networks (RN) and genomic data are needed to extract biological information for a better understanding of diseases, such as cancer, by improving the identification of entities and thereby leading to potential new therapeutic avenues. In this study, we confronted an automatically generated RN with gene expression profiles (GEP) from a cohort of multiple myeloma (MM) patients and normal individuals using global reasoning on the RN causality to identify key-nodes. We modeled each patient by his or her GEP, the RN and the possible automatically detected repairs needed to establish a coherent flow of the information that explains the logic of the GEP. These repairs could represent cancer mutations leading to GEP variability. With this reasoning, unmeasured protein states can be inferred, and we can simulate the impact of a protein perturbation on the RN behavior to identify therapeutic targets. We showed that JUN/FOS and FOXM1 activities are altered in almost all MM patients and identified two survival markers for MM patients. Our results suggest that JUN/FOS-activation has a strong impact on the RN in view of the whole GEP, whereas FOXM1-activation could be an interesting way to perturb an MM subgroup identified by our method.
The activation of PPARγ by 2,4,6-Octatrienoic acid protects human keratinocytes from UVR-induced damages
Authors: Flori Enrica , Mastrofrancesco Arianna , Kovacs Daniela , Bellei Barbara , Briganti Stefania , Maresca Vittoria , Cardinali Giorgia , Picardo Mauro 
Published: August 2017

AbstractIncreasing attention is addressed to identify products able to enhance skin photoprotection and to prevent skin carcinogenesis. Several studies have demonstrated that the α-melanocyte stimulating hormone (αMSH), acting on a functional MC1R, provides a photoprotective effect by inducing pigmentation, antioxidants and DNA repair. We discovered a link between αMSH and the nuclear receptor Peroxisome Proliferator-Activated Receptor-γ (PPARγ), suggesting that some of the αMSH protective effects may be dependent on PPARγ transcriptional activity. Moreover, we demonstrated that the activation of PPARγ by the parrodiene 2,4,6-octatrienoic acid (Octa) induces melanogenesis and antioxidant defence in human melanocytes and counteracts senescence-like phenotype in human fibroblasts. In this study, we demonstrate that the activation of PPARγ by Octa exerts a protective effect against UVA- and UVB-induced damage on normal human keratinocytes (NHKs), the major target cells of UV radiation. Octa promotes the antioxidant defence, augments DNA repair and reduces the induction of proteins involved in UV-induced DNA damage response. Our results contribute to deepen the analysis of the αMSH/PPARγ connection and suggest perspectives for the development of new molecules and formulations able to prevent cutaneous UV damage by acting on the different skin cell populations through PPARγ activation.
Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities
Authors: Di Pietro Valentina , Lazzarino Giacomo , Amorini Angela Maria , Signoretti Stefano , Hill Lisa J. , Porto Edoardo , Tavazzi Barbara , Lazzarino Giuseppe , Belli Antonio 
Published: August 2017

AbstractMitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.
The efficacy of biliary and serum macrophage inhibitory cytokine-1 for diagnosing biliary tract cancer
Authors: Sugimoto Mitsuru , Takagi Tadayuki , Konno Naoki , Suzuki Rei , Asama Hiroyuki , Watanabe Ko , Nakamura Jun , Waragai Yuichi , Kikuchi Hitomi , Takasumi Mika , Sato Yuki , Hikichi Takuto , Ohira Hiromasa 
Published: August 2017

AbstractThe serum macrophage inhibitory cytokine-1 (MIC-1) levels are elevated in some inflammatory conditions and cancers. We thus compared the levels of biliary and serum MIC-1 and conventional tumour markers between 23 biliary tract cancer (BTC) patients (malignant group) and 29 benign biliary disease patients (benign group) and found that all markers were significantly elevated in the malignant group. The levels of two markers were higher in early BTC (Stage I/II, n = 15) than in the benign group: biliary MIC-1 [12 (0–2153) vs. 678 (0–4429) pg/ml, P < 0.01] and serum CA19–9 [13 (2–15,682) vs. 45.1 (2–10,478) U/ml, P = 0.02]. A receiver operating characteristic curve analysis revealed that the area under the curve for biliary MIC-1 was greater than that for serum CA19-9 (0.77 vs. 0.73). The cut-off value for biliary MIC-1 in diagnosing early BTC was 581.6 pg/ml, and this value yielded a sensitivity, specificity and accuracy of 71.4%, 82.8%, and 79.1%, respectively. The sensitivity of biliary MIC-1 for diagnosing early BTC was superior to that of biliary cytology (71.4% vs. 8.33%, P < 0.01), and the combination of serum MIC-1 with CA19-9 (cut-off value = 4021.2 pg/ml, 42.4 U/ml) was useful for screening BTC (sensitivity = 82.6%, specificity = 72.4%). In conclusion, biliary MIC-1 can effectively diagnose early BTC.
Genome-wide comparative analyses of correlated and uncorrelated phenotypes identify major pleiotropic variants in dairy cattle
Authors: Xiang Ruidong , MacLeod Iona M. , Bolormaa Sunduimijid , Goddard Michael E. 
Published: August 2017

AbstractWhile single nucleotide polymorphisms (SNPs) associated with multiple phenotype have been reported, the knowledge of pleiotropy of uncorrelated phenotype is minimal. Principal components (PCs) and uncorrelated Cholesky transformed traits (CT) were constructed using 25 raw traits (RTs) of 2841 dairy bulls. Multi-trait meta-analyses of single-trait genome-wide association studies for RT, PC and CT in bulls were validated in 6821 cows. Most PCs and CTs had substantial estimates of heritability, suggesting that genes affect phenotype via diverse pathways. Phenotypic orthogonalizations did not eliminate pleiotropy: the meta-analysis achieved an agreement of significant pleiotropic SNPs (p < 1 × 10−5, n = 368) between RTs (416), PCs (466) and CTs (425). From this overlap we identified 21 lead SNPs with 100% validation rate containing two clusters: one consisted of DGAT1 (chr14:1.8 M+), MGST1 (chr5:93 M+), PAEP (chr11:103 M+) and GPAT4 (chr27:36 M+) affecting protein, milk and fat yield and the other included CSN2 (chr6:87 M+), MUC1 (chr3:15.6 M), GHR (chr20:31.2 M+) and SDC2 (chr14:70 M+) affecting protein and milk yield. Combining beef cattle data identified correlated SNPs representing CAPN1 (chr29:44 M+) and CAST (chr 7:96 M+) loci affecting beef tenderness, showing pleiotropic effects in dairy cattle. Our findings show that SNPs with a large effect on one trait are likely to have small effects on other uncorrelated traits.