bluuebunny/crossref_metadata_2025_split huggingface dataset:
TonEBP suppresses IL-10-mediated immunomodulation
Authors: Choi Soo Youn , Lee Hwan Hee , Lee Jun Ho , Ye Byeong Jin , Yoo Eun Jin , Kang Hyun Je , Jung Gyu Won , An Seung Min , Lee-Kwon Whaseon , Chiong Mario , Lavandero Sergio , Kwon Hyug Moo 
Published: May 2016

AbstractTonEBP is a key transcriptional activator of M1 phenotype in macrophage, and its high expression is associated with many inflammatory diseases. During the progression of the inflammatory responses, the M1 to M2 phenotypic switch enables the dual role of macrophages in controlling the initiation and resolution of inflammation. Here we report that in human and mouse M1 macrophages TonEBP suppresses IL-10 expression and M2 phenotype. TonEBP knockdown promoted the transcription of the IL-10 gene by enhancing chromatin accessibility and Sp1 recruitment to its promoter. The enhanced expression of M2 genes by TonEBP knockdown was abrogated by antagonism of IL-10 by either neutralizing antibodies or siRNA-mediated silencing. In addition, pharmacological suppression of TonEBP leads to similar upregulation of IL-10 and M2 genes. Thus, TonEBP suppresses M2 phenotype via downregulation of the IL-10 in M1 macrophages.
Synthesis of a highly water-soluble acacetin prodrug for treating experimental atrial fibrillation in beagle dogs
Authors: Liu Hui , Wang Ya-Jing , Yang Lei , Zhou Mei , Jin Man-Wen , Xiao Guo-Sheng , Wang Yan , Sun Hai-Ying , Li Gui-Rong 
Published: May 2016

AbstractWe previously reported that duodenal administration of the natural flavone acacetin can effectively prevent the induction of experimental atrial fibrillation (AF) in canines; however, it may not be used intravenously to terminate AF due to its poor water-solubility. The present study was to design a water-soluble prodrug of acacetin and investigate its anti-AF effect in beagle dogs. Acacetin prodrug was synthesized by a three-step procedure. Aqueous solubility, bioconversion and anti-AF efficacy of acacetin prodrug were determined with different methodologies. Our results demonstrated that the synthesized phosphate sodium salt of acacetin prodrug had a remarkable increase of aqueous solubility in H2O and clinically acceptable solution (5% glucose or 0.9% NaCl). The acacetin prodrug was effectively converted into acacetin in ex vivo rat plasma and liver microsome and in vivo beagle dogs. Intravenous infusion of acacetin prodrug (3, 6 and 12 mg/kg) terminated experimental AF without increasing ECG QTc interval in beagle dogs. The intravenous LD50 of acacetin prodrug was 721 mg/kg in mice. Our preclinical study indicates that the synthesized acacetin prodrug is highly water-soluble and safe; it effectively terminates experimental AF in beagle dogs and therefore may be a promising drug candidate for clinical trial to treat patients with acute AF.
Soil metaproteomics reveals an inter-kingdom stress response to the presence of black truffles
Authors: Zampieri Elisa , Chiapello Marco , Daghino Stefania , Bonfante Paola , Mello Antonietta 
Published: May 2016

AbstractFor some truffle species of the Tuber genus, the symbiotic phase is often associated with the presence of an area of scant vegetation, commonly known as the brûlé, around the host tree. Previous metagenomics studies have identified the microorganisms present inside and outside the brûlé of a Tuber melanosporum truffle-ground, but the molecular mechanisms that operate in this ecological niche remain to be clarified. To elucidate the metabolic pathways present in the brûlé, we conducted a metaproteomics analysis on the soil of a characterized truffle-ground and cross-referenced the resulting proteins with a database we constructed, incorporating the metagenomics data for the organisms previously identified in this soil. The soil inside the brûlé contained a larger number of proteins and, surprisingly, more proteins from plants, compared with the soil outside the brûlé. In addition, Fisher’s Exact Tests detected more biological processes inside the brûlé; these processes were related to responses to multiple types of stress. Thus, although the brûlé has a reduced diversity of plant and microbial species, the organisms in the brûlé show strong metabolic activity. Also, the combination of metagenomics and metaproteomics provides a powerful tool to reveal soil functioning.
Social stress increases the susceptibility to infection in the ant Harpegnathos saltator
Authors: Schneider Sebastian A. , Scharffetter Charlotte , Wagner Anika E. , Boesch Christine , Bruchhaus Iris , Rimbach Gerald , Roeder Thomas 
Published: May 2016

AbstractAggressive interactions between members of a social group represent an important source of social stress with all its negative follow-ups. We used the ponerine ant Harpegnathos saltator to study the effects of frequent aggressive interactions on the resistance to different stressors. In these ants, removal or death of reproducing animals results in a period of social instability within the colony that is characterized by frequent ritualized aggressive interactions leading to the establishment of a new dominance structure. Animals are more susceptible to infections during this period, whereas their resistance against other stressors remained unchanged. This is associated with a shift from glutathione-S-transferase activities towards glutathione peroxidase activities, which increases the antioxidative capacity at the expense of their immune competence.
The efficacy of contrast-enhanced harmonic endoscopic ultrasonography in diagnosing gallbladder cancer
Authors: Sugimoto Mitsuru , Takagi Tadayuki , Konno Naoki , Suzuki Rei , Asama Hiroyuki , Hikichi Takuto , Watanabe Ko , Waragai Yuichi , Kikuchi Hitomi , Takasumi Mika , Ohira Hiromasa 
Published: May 2016

AbstractThe aim of this study was to review the efficacy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in diagnosing gallbladder (GB)-protruded lesions. Thirty-eight patients underwent CH-EUS for the diagnosis of GB-protruded lesions. Twenty-four patients whose major axes of their largest lesions were longer than 10 mm were recruited. The ability of CH-EUS to diagnose malignant or benign lesions was reviewed. We treated lesions with brindled enhanced patterns as malignant and those with uniformly enhanced or unenhanced patterns as benign. Furthermore, three gastroenterologists who were not familiar with pancreaticobiliary EUS compared the diagnostic abilities of CH-EUS and conventional EUS using photographs. The sensitivity, specificity and malignant accuracy of CH-EUS were 100, 94.4 and 95.8%, respectively. The number of lesions that presented with enhanced patterns was significantly different between the malignant lesions and the benign lesions (P < 0.001). In the comparison of diagnostic abilities between CH-EUS and conventional EUS by the three gastroenterologists, CH-EUS was significantly superior to conventional EUS in terms of sensitivity, specificity and accuracy (76.1 vs. 42.9%, P = 0.029; 66.7 vs. 39.2%, P = 0.005; and 69.4 vs. 40.3%, P < 0.001; respectively). In conclusion, CH-EUS was useful for diagnosing malignant and benign GB-protruded lesions.
Atypical visual and somatosensory adaptation in schizophrenia-spectrum disorders
Authors: Andrade G N , Butler J S , Peters G A , Molholm S , Foxe J J 
Published: May 2016

AbstractNeurophysiological investigations in patients with schizophrenia consistently show early sensory processing deficits in the visual system. Importantly, comparable sensory deficits have also been established in healthy first-degree biological relatives of patients with schizophrenia and in first-episode drug-naive patients. The clear implication is that these measures are endophenotypic, related to the underlying genetic liability for schizophrenia. However, there is significant overlap between patient response distributions and those of healthy individuals without affected first-degree relatives. Here we sought to develop more sensitive measures of sensory dysfunction in this population, with an eye to establishing endophenotypic markers with better predictive capabilities. We used a sensory adaptation paradigm in which electrophysiological responses to basic visual and somatosensory stimuli presented at different rates (ranging from 250 to 2550 ms interstimulus intervals, in blocked presentations) were compared. Our main hypothesis was that adaptation would be substantially diminished in schizophrenia, and that this would be especially prevalent in the visual system. High-density event-related potential recordings showed amplitude reductions in sensory adaptation in patients with schizophrenia (N=15 Experiment 1, N=12 Experiment 2) compared with age-matched healthy controls (N=15 Experiment 1, N=12 Experiment 2), and this was seen for both sensory modalities. At the individual participant level, reduced adaptation was more robust for visual compared with somatosensory stimulation. These results point to significant impairments in short-term sensory plasticity across sensory modalities in schizophrenia. These simple-to-execute measures may prove valuable as candidate endophenotypes and will bear follow-up in future work.
Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report
Authors: Breen M S , Uhlmann A , Nday C M , Glatt S J , Mitt M , Metsalpu A , Stein D J , Illing N 
Published: May 2016

AbstractThe clinical presentation, course and treatment of methamphetamine (METH)-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in diagnosing MAP accurately at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH dependency without psychosis (MA;N=10) and healthy controls (N=10). First, we identified discrete groups of co-expressed genes (that is, modules) and tested them for functional annotation and phenotypic relationships to brain structure volumes, life events and psychometric measurements. We discovered one MAP-associated module involved in ubiquitin-mediated proteolysis downregulation, enriched with 61 genes previously found implicated in psychosis and SCZ across independent blood and post-mortem brain studies using convergent functional genomic (CFG) evidence. This module demonstrated significant relationships with brain structure volumes including the anterior corpus callosum (CC) and the nucleus accumbens. Furthermore, a second MAP and psychoticism-associated module involved in circadian clock upregulation was also enriched with 39 CFG genes, further associated with the CC. Subsequently, a machine-learning analysis of differentially expressed genes identified single blood-based biomarkers able to differentiate controls from methamphetamine dependents with 87% accuracy and MAP from MA subjects with 95% accuracy. CFG evidence validated a significant proportion of these putative MAP biomarkers in independent studies includingCLN3,FBP1,TBC1D2andZNF821(RNA degradation),ELK3andSINA3(circadian clock) andPIGFandUHMK1(ubiquitin-mediated proteolysis). Finally, focusing analysis on brain structure volumes revealed significantly lower bilateral hippocampal volumes in MAP subjects. Overall, these results suggest similar molecular and neurocognitive mechanisms underlying the pathophysiology of psychosis and SCZ regardless of substance abuse and provide preliminary evidence supporting the MAP paradigm as an exemplar for SCZ biomarker discovery.
A feminist genealogy of posthuman aesthetics in the visual arts
Authors: Ferrando Francesca 
Published: May 2016

AbstractThis article aims to reassemble a feminist genealogy of the posthuman in the arts, with a specific focus on the visual works conceived by female artists after the rise of what has been retrospectively defined as first-wave Feminism. Starting with the main avant-garde movements of the first half of the twentieth century—specifically, Futurism, Dadaism and Surrealism—this genealogy analyses the second-wave Feminism of the 1960s and 1970s, with its integral exploration of the body highlighted by performance art. Following this, it takes into account the third-wave Feminism of the 1990s and its radical re-elaboration of the self: from Cyberfeminism and its revisitation of technology, to the artistic insights offered, on the one side, by critical techno-orientalist readings of the futures, and on the other, by the political and social articulations of Afrofuturism and Chicanafuturism. Lastly, this genealogy accesses the ways contemporary female artists are dealing with gender, social media and the notion of embodiment, touching upon elements that will become of key importance in fourth-wave Feminism. This article is published as part of a collection dedicated to multi- and interdisciplinary perspectives on gender studies.
Science, technology and innovation indicators in policy-making: the Nigerian experience
Authors: Siyanbola Willie , Adeyeye Adedamola , Olaopa Olawale , Hassan Omowumi 
Published: May 2016

AbstractThis article provides a critical review of the process of formulating science, technology and innovation (STI) policy in Nigeria using scientific indicators. The attainment of development goals requires a painstaking process of policy-making based on scientific evidence derivable from relevant evidence. However, in many developing countries, there is a gap between policy and development priorities as most policies are not based on scientific facts either because they are unavailable or, where they exist, unreliable. Using a system analysis framework, the article brings into perspective the fundamental role played by STI indicators in providing scientific evidence for designing, formulating and implementing national innovation policy. This can serve as a framework for utilizing scientific evidence in policy-making in a developing country context. This article is published as part of a thematic collection on scientific advice to governments.
Hedgehog signaling enables nutrition-responsive inhibition of an alternative morph in a polyphenic beetle
Authors: Kijimoto Teiya , Moczek Armin P. 
Published: May 2016

Significance
Complex, nongradual responses to environmental conditions are commonplace in nature and perhaps most extreme in polyphenic insects where continuous variation in nutrition experienced in early development gives rise to discrete alternative castes or morphs. This research shows that the hedgehog (Hh) pathway has acquired a novel and highly unusual role in the nutrition-dependent regulation of polyphenic development of a beetle. Experimental repression of Hh signaling returns a highly discontinuous response to nutrition to its presumed ancestral, gradual state. Our results suggest that recruitment of the Hh signaling pathway may have been a key step in the evolution of trait thresholds and the corresponding origin of alternative phenotypes and complex allometries.
Achieving diverse and monoallelic olfactory receptor selection through dual-objective optimization design
Authors: Tian Xiao-Jun , Zhang Hang , Sannerud Jens , Xing Jianhua 
Published: May 2016

Significance
For sensitive smell detection, each mammalian olfactory sensory neurons need to express stochastically only one allele of 1 out of possibly more than 1,000 types of olfactory receptors. The mechanism for this monoallelic expression remains as one of the biggest unresolved questions for decades. Using mathematical modeling and computer simulations, we identified a three-layer regulation mechanism the olfactory system adopts to achieve single allelic expression and several other biological requirements such as maximizing the overall diversity of expressed olfactory receptors. The revealed mechanism provides insight for formulating biological processes as multiple-objective optimization problems.
Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals
Authors: Li Chun-Chun , Le Kang , Kato Jiro , Moss Joel , Vaughan Martha 
Published: May 2016

Significance
Transcriptional coactivator β-catenin promotes cell proliferation in development and tumorigenesis, via actions enhanced by PKA-catalyzed phosphorylation of its C-terminal region S675. Specific phosphorylation near the N terminus triggers ubiquitination and proteasomal degradation. Depletion of HeLa cell brefeldin A-inhibited guanine nucleotide-exchange factors (BIG)1 and/or BIG2 impaired β-catenin S675 phosphorylation and its transcriptional effects, as well as ADP-ribosylation factor activation-enhanced phospholipase D activity and vesicular trafficking, both required for restoration of transcriptional activation by appropriate BIG protein overexpression in depleted cells. We propose that interaction of β-catenin–bound BIG1 with BIG2 and its associated PKA complex, simultaneously or sequentially, are required for phosphorylation of S675, with nuclear entry of activated β-catenin followed by its acceleration of T-cell factor/lymphoid enhancer factor family gene transcription.
NLRC5/MHC class I transactivator is a target for immune evasion in cancer
Authors: Yoshihama Sayuri , Roszik Jason , Downs Isaac , Meissner Torsten B. , Vijayan Saptha , Chapuy Bjoern , Sidiq Tabasum , Shipp Margaret A. , Lizee Gregory A. , Kobayashi Koichi S. 
Published: May 2016

SignificanceTumor antigen presentation to CD8+T cells by MHC class I molecules is crucial for immune responses against cancers, whereas the loss of MHC class I is a common immune evasion strategy used by cancers. However, the molecular mechanisms leading to MHC class I deficiency have remained poorly defined. We demonstrate here that MHC class I transactivator (CITA)/NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5 (NLRC5) is a major target for cancer immune evasion. Reduced expression of MHC class I and related genes in cancer is frequently associated with genetic and epigenetic changes inNLRC5. The reducedNLRC5expression is linked to impaired CD8+T-cell activation and poor patient prognosis. These data indicate that CITA/NLRC5 is a novel prognostic marker and potential therapeutic target of cancers.
Silk-based blood stabilization for diagnostics
Authors: Kluge Jonathan A. , Li Adrian B. , Kahn Brooke T. , Michaud Dominique S. , Omenetto Fiorenzo G. , Kaplan David L. 
Published: May 2016

Significance
Both research and clinical care often require blood to be collected away from the laboratory setting. Remote collection presents a logistical and financial challenge, as it requires continuous access to portable cold storage. Although there has been a thrust to develop means to bypass the cold chain, available technologies such as dried spots, remain ineffective. Specifically, these methods fail to stabilize labile protein biomarkers against thermal damage. Herein we describe an alternative silk matrix encapsulation technique that overcomes these limitations and can be deployed using a simple air-drying approach. Potential clinical and research applications of this technology are far-reaching, and could ultimately decrease hospital burdens, improve patient compliance to monitoring, and open up new testing options for currently underserved populations.
Enhancing protein stability with extended disulfide bonds
Authors: Liu Tao , Wang Yan , Luo Xiaozhou , Li Jack , Reed Sean A. , Xiao Han , Young Travis S. , Schultz Peter G. 
Published: May 2016

Significance
This work describes a facile system for incorporating noncanonical amino acids containing long side-chain thiols using an expanded genetic code. These amino acids begin to overcome the distance and geometric constraints of the cysteine disulfide and can pair with cysteines to cross-link more remote sites in proteins. To demonstrate this notion, we constructed a library of random β-lactamase mutants containing these noncanonical amino acids and grew them at nonpermissive temperatures. We identified a mutant enzyme that is cross-linked by one such extended disulfide bond that has significantly enhanced thermal stability. This study suggests that an expanded set of amino acid building blocks can provide novel solutions to evolutionary challenges.
Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species
Authors: He Jiang , Zhou Ruobo , Wu Zhuhao , Carrasco Monica A. , Kurshan Peri T. , Farley Jonathan E. , Simon David J. , Wang Guiping , Han Boran , Hao Junjie , Heller Evan , Freeman Marc R. , Shen Kang , Maniatis Tom , Tessier-Lavigne Marc , Zhuang Xiaowei 
Published: May 2016

Significance
Actin, spectrin, and associated molecules form a submembrane periodic skeleton structure in neurons. In this study, we demonstrate that this membrane-associated periodic skeleton (MPS) is present in a broad range of neuronal cell types cultured from the central and peripheral nervous systems of rodents. The MPS structure is preferentially formed in axons compared with dendrites and is differentially regulated at the pre- and postsynaptic sites of neurons. Our data also suggest that MPS is conserved across a wide range of invertebrate and vertebrate animal species.
Analysis of reaction schemes using maximum rates of constituent steps
Authors: Motagamwala Ali Hussain , Dumesic James A. 
Published: May 2016

SignificanceThe design of active and selective catalysts is essential for a wide range of industrial applications and societal issues. A fundamental approach is to identify the key elementary steps and to elucidate the predicted reaction kinetics for potential reaction mechanisms. We present a methodology to analyze analytically the performance of catalytic reaction schemes by calculation of the maximum rates of the constituent steps. This proposed methodology can be used to identify the important transition states and adsorbed species, such that more detailed calculations can be carried out for these species, whereas more approximate methods can be used for the remaining species, thereby substantially reducing the computational time required to elucidate how catalyst performance is controlled by the fundamental surface chemistry.
Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge
Authors: Fischer Natalie , Sechet Emmanuel , Friedman Robin , Amiot Aurélien , Sobhani Iradj , Nigro Giulia , Sansonetti Philippe J. , Sperandio Brice 
Published: May 2016

SignificanceAntimicrobial peptides exert antimicrobial, antifungal, antiviral, and antiprotozoan activity. They are expressed at high concentrations at the intestinal mucosal surface, where they play a crucial role in intestinal homeostasis. Therefore, approaches aiming to boost expression of antimicrobial peptides represent a future therapeutic strategy to treat infections and dysbiosis-driven diseases in humans at a time of increasing incidence of antibiotic resistance.