bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival
Authors: Segatto Marco , Fittipaldi Raffaella , Pin Fabrizio , Sartori Roberta , Dae Ko Kyung , Zare Hossein , Fenizia Claudio , Zanchettin Gianpietro , Pierobon Elisa Sefora , Hatakeyama Shinji , Sperti Cosimo , Merigliano Stefano , Sandri Marco , Filippakopoulos Panagis , Costelli Paola , Sartorelli Vittorio , Caretti Giuseppina 
Published: November 2017

AbstractCancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia.
Short-term reward experience biases inference despite dissociable neural correlates
Authors: Fischer Adrian G. , Bourgeois-Gironde Sacha , Ullsperger Markus 
Published: November 2017

AbstractOptimal decision-making employs short-term rewards and abstract long-term information based on which of these is deemed relevant. Employing short- vs. long-term information is associated with different learning mechanisms, yet neural evidence showing that these two are dissociable is lacking. Here we demonstrate that long-term, inference-based beliefs are biased by short-term reward experiences and that dissociable brain regions facilitate both types of learning. Long-term inferences are associated with dorsal striatal and frontopolar cortex activity, while short-term rewards engage the ventral striatum. Stronger concurrent representation of reward signals by mediodorsal striatum and frontopolar cortex correlates with less biased, more optimal individual long-term inference. Moreover, dynamic modulation of activity in a cortical cognitive control network and the medial striatum is associated with trial-by-trial control of biases in belief updating. This suggests that counteracting the processing of optimally to-be-ignored short-term rewards and cortical suppression of associated reward-signals, determines long-term learning success and failure.
Molecular basis of AKAP79 regulation by calmodulin
Authors: Patel Neha , Stengel Florian , Aebersold Ruedi , Gold Matthew G. 
Published: November 2017

AbstractAKAP79/150 is essential for coordinating second messenger-responsive enzymes in processes including synaptic long-term depression. Ca2+ directly regulates AKAP79 through its effector calmodulin (CaM), but the molecular basis of this regulation was previously unknown. Here, we report that CaM recognizes a ‘1-4-7-8’ pattern of hydrophobic amino acids starting at Trp79 in AKAP79. Cross-linking coupled to mass spectrometry assisted mapping of the interaction site. Removal of the CaM-binding sequence in AKAP79 prevents formation of a Ca2+-sensitive interface between AKAP79 and calcineurin, and increases resting cellular PKA phosphorylation. We determined a crystal structure of CaM bound to a peptide encompassing its binding site in AKAP79. CaM adopts a highly compact conformation in which its open Ca2+-activated C-lobe and closed N-lobe cooperate to recognize a mixed α/310 helix in AKAP79. The structure guided a bioinformatic screen to identify potential sites in other proteins that may employ similar motifs for interaction with CaM.
Structural insights into the committed step of bacterial phospholipid biosynthesis
Authors: Li Zhenjian , Tang Yannan , Wu Yiran , Zhao Suwen , Bao Juan , Luo Yitian , Li Dianfan 
Published: November 2017

AbstractThe membrane-integral glycerol 3-phosphate (G3P) acyltransferase PlsY catalyses the committed and essential step in bacterial phospholipid biosynthesis by acylation of G3P, forming lysophosphatidic acid. It contains no known acyltransferase motifs, lacks eukaryotic homologs, and uses the unusual acyl-phosphate as acyl donor, as opposed to acyl-CoA or acyl-carrier protein for other acyltransferases. Previous studies have identified several PlsY inhibitors as potential antimicrobials. Here we determine the crystal structure of PlsY at 1.48 Å resolution, revealing a seven-transmembrane helix fold. Four additional substrate- and product-bound structures uncover the atomic details of its relatively inflexible active site. Structure and mutagenesis suggest a different acylation mechanism of ‘substrate-assisted catalysis’ that, unlike other acyltransferases, does not require a proteinaceous catalytic base to complete. The structure data and a high-throughput enzymatic assay developed in this work should prove useful for virtual and experimental screening of inhibitors against this vital bacterial enzyme.
Carrageenan catabolism is encoded by a complex regulon in marine heterotrophic bacteria
Authors: Ficko-Blean Elizabeth , Préchoux Aurélie , Thomas François , Rochat Tatiana , Larocque Robert , Zhu Yongtao , Stam Mark , Génicot Sabine , Jam Murielle , Calteau Alexandra , Viart Benjamin , Ropartz David , Pérez-Pascual David , Correc Gaëlle , Matard-Mann Maria , Stubbs Keith A. , Rogniaux Hélène , Jeudy Alexandra , Barbeyron Tristan , Médigue Claudine , Czjzek Mirjam , Vallenet David , McBride Mark J. , Duchaud Eric , Michel Gurvan 
Published: November 2017

AbstractMacroalgae contribute substantially to primary production in coastal ecosystems. Their biomass, mainly consisting of polysaccharides, is cycled into the environment by marine heterotrophic bacteria using largely uncharacterized mechanisms. Here we describe the complete catabolic pathway for carrageenans, major cell wall polysaccharides of red macroalgae, in the marine heterotrophic bacterium Zobellia galactanivorans. Carrageenan catabolism relies on a multifaceted carrageenan-induced regulon, including a non-canonical polysaccharide utilization locus (PUL) and genes distal to the PUL, including a susCD-like pair. The carrageenan utilization system is well conserved in marine Bacteroidetes but modified in other phyla of marine heterotrophic bacteria. The core system is completed by additional functions that might be assumed by non-orthologous genes in different species. This complex genetic structure may be the result of multiple evolutionary events including gene duplications and horizontal gene transfers. These results allow for an extension on the definition of bacterial PUL-mediated polysaccharide digestion.
Gαi is required for carvedilol-induced β1 adrenergic receptor β-arrestin biased signaling
Authors: Wang Jialu , Hanada Kenji , Staus Dean P. , Makara Michael A. , Dahal Giri Raj , Chen Qiang , Ahles Andrea , Engelhardt Stefan , Rockman Howard A. 
Published: November 2017

AbstractThe β1 adrenergic receptor (β1AR) is recognized as a classical Gαs-coupled receptor. Agonist binding not only initiates G protein-mediated signaling but also signaling through the multifunctional adapter protein β-arrestin. Some βAR ligands, such as carvedilol, stimulate βAR signaling preferentially through β-arrestin, a concept known as β-arrestin-biased agonism. Here, we identify a signaling mechanism, unlike that previously known for any Gαs-coupled receptor, whereby carvedilol induces the transition of the β1AR from a classical Gαs-coupled receptor to a Gαi-coupled receptor stabilizing a distinct receptor conformation to initiate β-arrestin-mediated signaling. Recruitment of Gαi is not induced by any other βAR ligand screened, nor is it required for β-arrestin-bias activated by the β2AR subtype of the βAR family. Our findings demonstrate a previously unrecognized role for Gαi in β1AR signaling and suggest that the concept of β-arrestin-bias may need to be refined to incorporate the selective bias of receptors towards distinct G protein subtypes.
Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses
Authors: Zhu Houze , Yan Huanhuan , Tang Na , Li Xinyan , Pang Pei , Li Hao , Chen Wenting , Guo Yu , Shu Shu , Cai You , Pei Lei , Liu Dan , Luo Min-Hua , Man Hengye , Tian Qing , Mu Yangling , Zhu Ling-Qiang , Lu Youming 
Published: November 2017

AbstractCholine acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival.
Physiological dynamics of stress contagion
Authors: Dimitroff Stephanie J. , Kardan Omid , Necka Elizabeth A. , Decety Jean , Berman Marc G. , Norman Greg J. 
Published: November 2017

AbstractCan viewing others experiencing stress create a “contagious” physiological stress response in the observer? To investigate second-hand stress, we first created a stimulus set of videos, which featured participants speaking under either minimal stress, high stress, or while recovering from stress. We then recruited a second set of participants to watch these videos. All participants (speakers and observers) were monitored via electrocardiogram. Cardiac activity of the observers while watching the videos was then analyzed and compared to that of the speakers. Furthermore, we assessed dispositional levels of empathy in observers to determine how empathy might be related to the degree of stress contagion. Results revealed that depending on the video being viewed, observers experienced differential changes in cardiac activity that were based on the speaker’s stress level. Additionally, this is the first demonstration that individuals high in dispositional empathy experience these physiological changes more quickly.
MiR-92a and miR-486 are potential diagnostic biomarkers for mercury poisoning and jointly sustain NF-κB activity in mercury toxicity
Authors: Ding Enmin , Guo Jun , Bai Ying , Zhang Hengdong , Liu Xin , Cai Wenyan , Zhong Lixin , Zhu Baoli 
Published: November 2017

AbstractOccupational and environmental exposure to mercury is a public health concern worldwide. Although the altered epigenetic regulatory features, such as microRNA, have been associated with mercury exposure, the underlying molecular mechanism is not well illuminated. This study aimed to confirm that hsa-miR-92a and hsa-miR-486 are novel diagnostic biomarkers of occupational mercury poisoning, and to explore the underlying mechanism of miR-92a and miR-486 in mercury toxicity. RT-qPCR assays and receiver operating characteristics curve analyses were conducted to confirm the diagnostic value of miR-92a and miR-486 as biomarkers of occupational mercury poisoning. Dual-luciferase assay was applied to confirm the target gene of miR-92a and miR-486 in vitro. Then, we established an in-vitro model where miR-92a and miR-486 were overexpressed or knocked down in HEK-293 and HUVEC cells. RT-qPCR and western blotting were used to analyze gene and protein expression levels. Cell apoptosis was determined by flow cytometry. Results show that miR-92a and miR-486 expression levels were up-regulated in workers exposed to occupational mercury. Upregulation of miR-92a and miR-486 may play a crucial role in mercury toxicity by jointly activating the NF-κB signaling pathway via targeting KLF4 and Cezanne, respectively.
Elevated blood pressure is associated with higher prevalence of low visual acuity among adolescent males in Northeast China
Authors: Zhao Miaomiao , Wang Wei , Yu Han , Ma Yunsheng , Zheng Liqiang , Zhang Lijuan , Wu Guiping , Sun Yingxian , Li Jue 
Published: November 2017

AbstractThe purpose of this study is to track the trends of low visual acuity (VA) from 2005 to 2014, and to investigate its associations with systemic blood pressure (BP) components among adolescents in Northeast China. A total of 55320 students of Han nationality aged 13 to 18 years were included. There has been a significant increase in the prevalence of low VA, with 31.3% in 2005, 40.2% in 2010 and 43.4% in 2014. In multivariable-adjusted logistic regression models, each 1-mm Hg increment in systolic BP (SBP) was associated with 0.8% (95% confidence interval [CI]: 0.1–1.6%), 0.5% (95% CI: 0.1–0.9%) and 1.1% (95% CI: 0.6–1.6%) increased odds of low VA for males in 2005, 2010 and 2014; each 1-mm Hg increment in pulse pressure (PP) was associated with 1.6% (95% CI: 0.7–2.5%), 0.8% (95% CI: 0.4–1.2%) and 1.2% (95% CI: 0.7–1.7%) increased odds of low VA. Higher PP categories had greater odds for low VA compared with the reference group. Similar associations were not observed for females. We conclude that higher prevalence of low VA was significantly associated with higher SBP and PP in males. Furthermore, there was a dose-dependent association between the prevalence of low VA and the levels of PP.
Stochastic fluctuations can reveal the feedback signs of gene regulatory networks at the single-molecule level
Authors: Jia Chen , Xie Peng , Chen Min , Zhang Michael Q. 
Published: November 2017

AbstractUnderstanding the relationship between spontaneous stochastic fluctuations and the topology of the underlying gene regulatory network is of fundamental importance for the study of single-cell stochastic gene expression. Here by solving the analytical steady-state distribution of the protein copy number in a general kinetic model of stochastic gene expression with nonlinear feedback regulation, we reveal the relationship between stochastic fluctuations and feedback topology at the single-molecule level, which provides novel insights into how and to what extent a feedback loop can enhance or suppress molecular fluctuations. Based on such relationship, we also develop an effective method to extract the topological information of a gene regulatory network from single-cell gene expression data. The theory is demonstrated by numerical simulations and, more importantly, validated quantitatively by single-cell data analysis of a synthetic gene circuit integrated in human kidney cells.
The role of reproductive isolation in allopolyploid speciation patterns: empirical insights from the progenitors of common wheat
Authors: Matsuoka Yoshihiro , Takumi Shigeo 
Published: November 2017

AbstractThe ability to cause reproductive isolation often varies among individuals within a plant species. We addressed whether such polymorphism influenced speciation of the allopolyploid common wheat (Triticum aestivum L., AABBDD genome) by evaluating the expression of pre-pollination (outcrossing potential) and post-pollination (crossability) barriers in Aegilops tauschii Coss. (the D genome progenitor). In total, 201 Ae. tauschii accessions representing the entire natural habitat range of the species were used for anther length measurement and artificial crosses with a Triticum turgidum L. (the AB genome progenitor) tester. Intraspecific comparisons showed that both barriers were more strongly expressed in the TauL1 lineage than in the TauL2 lineage. The ability of Ae. tauschii to cause reproductive isolation in the hybridisation with T. turgidum might have markedly influenced common wheat’s speciation by inducing lineage-associated patterns of gene flow. The TauL2 accessions with high potential for natural hybridisation with T. turgidum clustered in the southern coastal Caspian region. This provided phenotypic support for the derivation of the D genome of common wheat from southern Caspian populations. The present study underscored the importance of approaches that incorporate the genealogical and geographic structure of the parental species’ reproductive isolation in understanding the mechanism of plant allopolyploid speciation.
Two-Dimensional Co2S2 monolayer with robust ferromagnetism
Authors: Zhang Yun , Pang Jingman , Zhang Meiguang , Gu Xiao , Huang Li 
Published: November 2017

AbstractDesign and synthesis of two-dimensional (2D) materials with robust intrinsic ferromagnetism is highly desirable due to their potential applications in spintronics devices. In this work, we identify a new 2D cobalt sulfide (Co2S2) material by using first-principles calculations and particle swarm optimization (PSO) global structure search. We show that the 2D Co2S2 is most stable in the litharge type tetragonal structure with space group of P4/nmm. The elastic constants, phonon spectrum, and molecular dynamics simulation confirm its mechanical, dynamical and thermal stability, respectively. It is also found that Co2S2 monolayer is a ferromagnetic metal with a Curie temperature up to 404 K. In addition, we propose a feasible procedure to synthesize the Co2S2 monolayer by chemically exfoliating from bulk TlCo2S2 phase.
Liver-specific deletion of RORα aggravates diet-induced nonalcoholic steatohepatitis by inducing mitochondrial dysfunction
Authors: Kim Hyeon-Ji , Han Yong-Hyun , Na Hyelin , Kim Ju-Yeon , Kim Taewook , Kim Hye-Jin , Shin Chanseok , Lee Jung Weon , Lee Mi-Ock 
Published: November 2017

AbstractMitochondrial dysfunction may play a key role in the progression of steatosis to nonalcoholic steatohepatitis (NASH); however, the molecular mechanism that controls the structure and function of mitochondria in NASH is not clearly understood. Here, we demonstrated that RORα is a regulator of expression of Bnip3 and PGC-1α, and thereby enhances mitochondrial quality. First, we observed that liver-specific RORα knockout mice (RORα-LKO) were more susceptible to high-fat diet-induced NASH compared with control, probably due to mitochondrial dysfunction. Concordantly, mitochondrial fission in response to nutrient stimuli was abolished with downregulation of Bnip3 and phospho-Drp1 in the hepatocytes of RORα-LKO. RORα enhanced oxygen consumption rate and expression of genes associated with mitochondrial quality control. Finally, we observed the positive correlation of the expression levels of Bnip3 and PGC-1α with those of RORα in patients with steatohepatitis. Together, we demonstrated that RORα mediates mitochondrial quality under nutrient-overloaded conditions and propose RORα as a potential therapeutic target in treatment of NASH.
Picture Interpretation Test (PIT) 360°: An Innovative Measure of Executive Functions
Authors: Serino Silvia , Baglio Francesca , Rossetto Federica , Realdon Olivia , Cipresso Pietro , Parsons Thomas D. , Cappellini Giacomo , Mantovani Fabrizia , De Leo Gianluca , Nemni Raffaello , Riva Giuseppe 
Published: November 2017

AbstractThe assessment of executive functions poses researchers with several challenges related to both the complexity of the construct of executive functions itself and/or the methodological difficulties related to its evaluation. The main objective of the current study was to evaluate a 360° version of an ecologically valid assessment called the Picture Interpretation Test (PIT). Participants included 19 patients with Parkinson’s disease (PD) and 19 healthy controls. All participants endorsed globally positive experiences of the PIT 360°. Furthermore, findings indicated that patients with PD took longer to correctly interpret the PIT 360° scene and tended to significantly focus on details of the 360° scene instead of the most informative elements. The time needed for a correct interpretation of the presented scene also correlated significantly with performance in conventional paper and pencil tests of executive functions for patients with PD. Classification analysis indicated the potential of the PIT 360° for distinguishing between patients with PD and healthy controls. Overall, these data provide preliminary evidence in support of the PIT 360° for evaluating executive functions.
Possible mechanisms of control of Fusarium wilt of cut chrysanthemum by Phanerochaete chrysosporium in continuous cropping fields: A case study
Authors: Li Ping , Chen Jingchao , Li Yi , Zhang Kun , Wang Hailei 
Published: November 2017

AbstractContinuous cropping is a universal challenge in agriculture because it has adverse physiological effects on plants, resulting in stunting, inferior quality, and even massive loss in harvest due to diseases. In this study, Phanerochaete chrysosporium was inoculated into the field in which cut chrysanthemum had already been continuously cropped for five years to control wilt disease. After 120 days of cultivation, the addition of P. chrysosporium significantly improved the physiological status of plants and changed the bacterial and fungal community structure in the soil. The bacterial quantity in the treatment increased by 1.76 times, but the fungal quantity, especially the quantity of Fusarium oxysporum, decreased significantly in comparison with the control. The investigation into the mechanisms of control of Fusarium wilt of cut chrysanthemum by P. chrysosporium showed that P. chrysosporium in soil can inhibit the growth of F. oxysporum and decrease p-hydroxybenzoic acid (HA), which stimulates the propagation of F. oxysporum. Based on current evidence, the inhibition by P. chrysosporium and change in HA appear to be the main causes of the alleviation of wilt disease in the treatment. Other factors, such as nutrients, might also have an influence on the wilt disease of cut chrysanthemum.
T helper cells with specificity for an antigen in cardiomyocytes promote pressure overload-induced progression from hypertrophy to heart failure
Authors: Gröschel Carina , Sasse André , Röhrborn Charlotte , Monecke Sebastian , Didié Michael , Elsner Leslie , Kruse Vanessa , Bunt Gertrude , Lichtman Andrew H. , Toischer Karl , Zimmermann Wolfram-Hubertus , Hasenfuß Gerd , Dressel Ralf 
Published: November 2017

AbstractWe investigated whether CD4+-T cells with specificity for an antigen in cardiomyocytes promote the progression from hypertrophy to heart failure in mice with increased pressure load due to transverse aortic constriction (TAC). OT-II mice expressing a transgenic T cell receptor (TCR) with specificity for ovalbumin (OVA) on CD4+-T cells and cMy-mOVA mice expressing OVA on cardiomyocytes were crossed. The resulting cMy-mOVA-OT-II mice did not display signs of spontaneous autoimmunity despite the fact that their OVA-specific CD4+-T cells were not anergic. After TAC, progression to heart failure was significantly accelerated in cMy-mOVA-OT-II compared to cMy-mOVA mice. No OVA-specific antibodies were induced in response to TAC in cMy-mOVA-OT-II mice, yet more CD3+T cells infiltrated their myocardium when compared with TAC-operated cMy-mOVA mice. Systemically, the proportion of activated CD4+-T cells with a Th1and Th17cytokine profile was increased in cMy-mOVA-OT-II mice after TAC. Thus, T helper cells with specificity for an antigen in cardiomyocytes can directly promote the progression of heart failure in response to pressure overload independently of autoantibodies.