bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of contested multilateralism for global constitutionalism
Authors: FOLLESDAL ANDREAS
Published: November 2016

The article considers implications of contested multilateralism for the processes and normative standards of global constitutionalism. The focus is primarily on aspects of CM regarded as a mode of constitutional change, considering what to make of such a form of ‘extra-constitutional’ procedure. Research challenges for political science, law and normative political theory are identified. Challenges by CM to the stability of international law are argued to be overdrawn. Of greater concern is that CM lends itself to piecemeal adjustments rather than reforms with an eye to the systemic effects. However, these worries must be tempered by the non-ideal nature of the present legal structure which should make us wary of imposing normative standards drawn from settings where institutions are fully just and generally complied with.
The Automaticity of Affordance of Dangerous Object
Authors: Zhao Liang
Published: November 2016

Objects observation automatically elicits the activation of a reach-to-grasp response specifically directed to interact with the object, which is termed affordance. Murphy, van Velzen, and de Fockert (2012) found that only when an irrelevant object receives sufficient attention, it can potentiate an action. However, it remains unclear whether the dangerous object would afford an action when it receives insufficient attention. In this study, we manipulated the perceptual load in a letter identification task. Participants were required to identify a target letter with the right or left hand while ignoring a neutral or dangerous graspable object. The target letter was presented either on its own (low perceptual load), alongside five non-target letters (high load), or alongside eight non-target letters (super high load). Under the low perceptual load, for both neutral and dangerous object, responses were faster when the action afforded by the ignored object was congruent (vs. incongruent) with the current target response (t(27) = 4.44, p < .001; t(27) = 7.99, p < .001, respectively). However, during the high perceptual load, for dangerous object, responses were slower when the action afforded by the ignored object was congruent (vs. incongruent) with the current target response (t(27) = 4.97, p < .001). There was not any effect for both neutral object and dangerous object under super high perceptual load. These results suggest the affordance of dangerous object is also sensitive to the perceptual load. An irrelevant dangerous object can’t potentiate an action if it receives insufficient attention.
The Great Enrichment:A Humanistic and Social Scientific Account
Authors: McCloskey Deirdre Nansen
Published: November 2016

From 1800 to the present the average person on the planet has been enriched in real terms by a factor of 10, or some 900 percent. In the ever-rising share of places from Belgium to Botswana, and now in China and India, that have agreed to the Bourgeois Deal—“Let me earn profits from creative destruction in the first act, and by the third act I will make all of you rich”—the factor is 30 in conventional terms and, if allowing for improved quality of goods and services, such as in improved glass and autos, or improved medicine and higher education, a factor of 100. That is, the reward from allowing ordinary people to have a go, the rise at first in northwestern Europe and then worldwide of economic liberty and social dignity, eroding ancient hierarchy and evading modern regulation, has been anything from 2,900 to 9,900 percent. What needs to be explained in a modern social science history is not the Industrial Revolution(s) but the Great Enrichment, one or two orders of magnitude larger than any previous change in human history. The article takes seriously the lesson of comparative history that Europe was not unique until 1700 and argues that ideas—specifically Bourgeois liberal ideas—not capital or institutions, made the modern world.
Not a Knowledge Bank: The Divided History of Development Economics and Development Organizations
Authors: Alacevich Michele
Published: November 2016

Development economics was born as a distinct disciplinary field in the aftermath of World War II, when the development of so-called Third World countries, due to the dynamics of decolonization and the Cold War, became an international priority. At the institutional level, the birth of development economics was paralleled by the reorientation of the International Bank for Reconstruction and Development (so-called the World Bank) from the support of European reconstruction to funding development policies worldwide. Not surprisingly, the paths of the Bank and of pioneers of development economics often crossed, and it is fair to say that the Bank and the new discipline—from the perspective of the history and sociology of social sciences—are part of the same story. Indeed, one would think that the Bank was the natural place for the breeding of development economics. This seems coherent with the image we have of the Bank today: the reign of economists. Yet, for most of the years when development theory was shaped, the Bank, although very active in development policies worldwide, was remarkably silent in the field of development economics. This paper will connect the study of economic ideas and economists in international organizations with the history of economic policies. Based on previously untapped archival sources, it will discuss how the history of development economics and of development organizations—and especially the largest among them, that is, the World Bank—proceeded separated for a long stretch of time, and how they later converged.
BeforeThe Philadelphia Negro: Residential Segregation in a Nineteenth-Century Northern City
Authors: Logan John R. , Bellman Benjamin
Published: November 2016

Although some scholars treat racial residential segregation in northern cities as a twentieth-century phenomenon, recent research on New York and Chicago has shown that black-white segregation was already high and rising by 1880. We draw on data from the Philadelphia Social History Project and other new sources to study trends in this city as far back as 1850 and extending to 1900, a time when DuBois had completed his epic study of The Philadelphia Negro. Segregation of “free negroes” in Philadelphia was high even before the Civil War but did not increase as the total and black populations grew through 1900. Geocoded information from the full-count data from the 1880 Census makes it possible to map the spatial configuration of black residents in fine detail. At the scale of the street segment, segregation in that year was extraordinarily high, reflecting a micropattern in which many blacks lived in alleys and short streets. Although there was considerable class variation in the black community, higher-status black households lived in areas that were little different in racial and class composition than lower-status households.
Improving Carbon Cycle Projections for Better Carbon Management
Authors: Xiao Jingfeng , Luo Yiqi , Shrestha Gyami
Published: November 2016

Workshop on Development of Predictive Carbon Cycle Science;
College Park, Maryland, 7–9 March 2016
CD169+ macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection
Authors: Shaabani Namir , Duhan Vikas , Khairnar Vishal , Gassa Asmae , Ferrer-Tur Rita , Häussinger Dieter , Recher Mike , Zelinskyy Gennadiy , Liu Jia , Dittmer Ulf , Trilling Mirko , Scheu Stefanie , Hardt Cornelia , Lang Philipp A , Honke Nadine , Lang Karl S
Published: November 2016

Upon infection with persistence-prone virus, type I interferon (IFN-I) mediates antiviral activity and also upregulates the expression of programmed death ligand 1 (PD-L1), and this upregulation can lead to CD8+ T-cell exhaustion. How these very diverse functions are regulated remains unknown. This study, using the lymphocytic choriomeningitis virus, showed that a subset of CD169+ macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169+ macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus. Lack of CD169+ macrophages also limited the IFN-I-dependent expression of PD-L1. Enhanced viral replication in the absence of PD-L1 led to persistence of virus and prevented CD8+ T-cell exhaustion. As a consequence, mice exhibited severe immunopathology and died quickly after infection. Therefore, CD169+ macrophages are important contributors to the IFN-I response and thereby influence antiviral activity, CD8+ T-cell exhaustion and immunopathology.
Phospholipase D1-regulated autophagy supplies free fatty acids to counter nutrient stress in cancer cells
Authors: Cai Ming , He Jingquan , Xiong Jian , Tay Li Wei Rachel , Wang Ziqing , Rog Colin , Wang Jingshu , Xie Yizhao , Wang Guobin , Banno Yoshiko , Li Feng , Zhu Michael , Du Guangwei
Published: November 2016

Cancer cells utilize flexible metabolic programs to maintain viability and proliferation under stress conditions including nutrient deprivation. Here we report that phospholipase D1 (PLD1) participates in the regulation of metabolic plasticity in cancer cells. PLD1 activity is required for cancer cell survival during prolonged glucose deprivation. Blocking PLD1 sensitizes cancer cells to glycolysis inhibition by 2-deoxy-D-glucose (2-DG) and results in decreased autophagic flux, enlarged lysosomes, and increased lysosomal pH. Mechanistically, PLD1-regulated autophagy hydrolyzes bulk membrane phospholipids to supply fatty acids (FAs) for oxidation in mitochondria. In low glucose cultures, the blockade of fatty acid oxidation (FAO) by PLD1 inhibition suppresses adenosine triphosphate (ATP) production and increases reactive oxygen species (ROS), leading to cancer cell death. In summary, our findings reveal a novel role of PLD1 in sustaining cancer cell survival during metabolic stress, and suggest PLD1 as a potential target for anticancer metabolism therapy.
PAR2 regulates regeneration, transdifferentiation, and death
Authors: Piran Ron , Lee Seung-Hee , Kuss Pia , Hao Ergeng , Newlin Robbin , Millán José Luis , Levine Fred
Published: November 2016

Understanding the mechanisms by which cells sense and respond to injury is central to developing therapies to enhance tissue regeneration. Previously, we showed that pancreatic injury consisting of acinar cell damage+β-cell ablation led to islet cell transdifferentiation. Here, we report that the molecular mechanism for this requires activating protease-activated receptor-2 (PAR2), a G-protein-coupled receptor. PAR2 modulation was sufficient to induce islet cell transdifferentiation in the absence ofβ-cells. Its expression was modulated in an islet cell type-specific manner in murine and human type 1 diabetes (T1D). In addition to transdifferentiation, PAR2 regulatedβ-cell apoptosis in pancreatitis. PAR2’s role in regeneration is broad, as mice lacking PAR2 had marked phenotypes in response to injury in the liver and in digit regeneration following amputation. These studies provide a pharmacologically relevant target to induce tissue regeneration in a number of diseases, including T1D.
Monocytic thrombomodulin promotes cell adhesion through interacting with its ligand, Lewisy
Authors: Lin Wei‐Ling , Chen Chia‐Chi , Shi Guey‐Yueh , Ma Chih‐Yuan , Chang Chuan‐Fa , Wu Hua‐Lin
Published: November 2016

The leukocyte adhesion cascade involves multiple events that efficiently localize circulating leukocytes into the injured sites to mediate inflammatory responses. From rolling to firm adhesion, the interactions between adhesion molecules have pivotal roles in increasing the avidity of leukocytes to endothelial cells. Thrombomodulin (TM), an essential anticoagulant protein in the vasculature, is also expressed on leukocytes. We previously demonstrated that Lewisy (Ley), a specific ligand of TM, is upregulated in inflamed endothelium and is involved in leukocyte adhesion. The current study aimed to investigate whether leukocyte‐expressed TM promotes cell adhesion by interacting with Ley. Using human monocytic THP‐1 cells as an in vitro cell model, we showed that TM increases THP‐1 cell adhesion to inflamed endothelium as well as to Ley‐immobilized surface. When THP‐1 adhered to activated endothelium and Ley‐immobilized surface, the TM distribution became polarized. Addition of soluble Ley to a suspension of THP‐1 cells with TM expression triggered an increase in the level of phosphorylated p38 mitogen‐activated protein kinase (MAPK), which enabled THP‐1 to adhere firmly to intercellular adhesion molecule (ICAM)‐1 by activating β2 integrins. In vivo, macrophage infiltration and neointima formation following arterial ligation‐induced vascular injury were higher in wild‐type TM (TMflox/flox) than in myeloid‐specific TM‐deficient (LysMcre/TMflox/flox) mice. Taken together, these results suggest a novel function for TM as an adhesion molecule in monocytes, where it enhances cell adhesion by binding Ley, leading to β2 integrin activation via p38 MAPK.
The flux qubit revisited to enhance coherence and reproducibility
Authors: Yan Fei , Gustavsson Simon , Kamal Archana , Birenbaum Jeffrey , Sears Adam P , Hover David , Gudmundsen Ted J. , Rosenberg Danna , Samach Gabriel , Weber S , Yoder Jonilyn L. , Orlando Terry P. , Clarke John , Kerman Andrew J. , Oliver William D.
Published: November 2016

The scalable application of quantum information science will stand on reproducible and controllable high-coherence quantum bits (qubits). Here, we revisit the design and fabrication of the superconducting flux qubit, achieving a planar device with broad-frequency tunability, strong anharmonicity, high reproducibility and relaxation times in excess of 40 μs at its flux-insensitive point. Qubit relaxation times T1 across 22 qubits are consistently matched with a single model involving resonator loss, ohmic charge noise and 1/f-flux noise, a noise source previously considered primarily in the context of dephasing. We furthermore demonstrate that qubit dephasing at the flux-insensitive point is dominated by residual thermal-photons in the readout resonator. The resulting photon shot noise is mitigated using a dynamical decoupling protocol, resulting in T2≈85 μs, approximately the 2T1 limit. In addition to realizing an improved flux qubit, our results uniquely identify photon shot noise as limiting T2 in contemporary qubits based on transverse qubit–resonator interaction.
Following lithiation fronts in paramagnetic electrodes with in situ magnetic resonance spectroscopic imaging
Authors: Tang Mingxue , Sarou-Kanian Vincent , Melin Philippe , Leriche Jean-Bernard , Ménétrier Michel , Tarascon Jean-Marie , Deschamps Michaël , Salager Elodie
Published: November 2016

Li-ion batteries are invaluable for portable electronics and vehicle electrification. A better knowledge of compositional variations within the electrodes during battery operation is, however, still needed to keep improving their performance. Although essential in the medical field, magnetic resonance imaging of solid paramagnetic battery materials is challenging due to the short lifetime of their signals. Here we develop the scanning image-selected in situ spectroscopy approach, using the strongest commercially available magnetic field gradient. We demonstrate the 7Li magnetic resonance spectroscopic image of a 5 mm-diameter operating battery with a resolution of 100 μm. The time-resolved image-spectra enable the visualization in situ of the displacement of lithiation fronts inside thick paramagnetic electrodes during battery operation. Such observations are critical to identify the key limiting parameters for high-capacity and fast-cycling batteries. This non-invasive technique also offers opportunities to study devices containing paramagnetic materials while operating.
Recent developments in the diagnosis and management of tuberculosis
Authors: Sulis Giorgia , Centis Rosella , Sotgiu Giovanni , D’Ambrosio Lia , Pontali Emanuele , Spanevello Antonio , Matteelli Alberto , Zumla Alimuddin , Migliori Giovanni Battista
Published: November 2016

Tuberculosis (TB) is a major public health issue worldwide, with ~9.6 million new incident cases and 1.5 million deaths in 2014. The End-TB Strategy launched by the World Health Organization in the context of the post-2015 agenda aims to markedly abate the scourge of TB towards global elimination, by improving current diagnostic and therapeutic practices, promoting preventative interventions, stimulating government commitment and increased financing, and intensifying research and innovation. The emergence and spread of multidrug-resistant strains is currently among the greatest concerns, which may hinder the achievement of future goals. It is crucial that primary healthcare providers are sufficiently familiar with the basic principles of TB diagnosis and care, to ensure early case detection and prompt referral to specialised centres for treatment initiation and follow-up. Given their special relationship with patients, they are in the best position to promote educational interventions and identify at-risk individuals as well as to improve adherence to treatment.
Adaptive capacities from survival to stress responses of two isogenic lines of rainbow trout fed a plant-based diet
Authors: Sadoul B. , Foucard A. , Valotaire C. , Labbé L. , Goardon L. , LeCalvez J. M. , Médale F. , Quillet E. , Dupont-Nivet M. , Geurden I. , Prunet P. , Colson V.
Published: November 2016

The composition of feed for farmed salmonids has strongly evolved during the last decades due to the substitution of fishery-derived fish oil and fishmeal by ingredients of plant origin. Little information is available regarding the effects of this transition on adaptive capacities in fish. Two rainbow trout isogenic lines, known for their divergent ability to grow on a plant-based diet (PBD), were fed for seven months from first feeding either a fully PBD or a control marine-resources diet and were compared for their growing and survival capacities over time and their behavioral and stress responses at similar sizes but different ages. Although fish displayed similar appetitive behaviour, the two lines were highly affected by the PBD translated in decreased growth and apathetic behaviour, but also stronger stress responses displayed by stronger cortisol increases and more stress-related behaviour when isolated. The two lines were found to be similarly sensitive to a PBD for the assessed stress-related parameters, but one line displayed a lower survival during the early rearing period. Overall, these results suggest that a PBD supplied to fish from the alevin stage has strong effects on physiological and behavioural parameters, with possible impairment of fish welfare, but also genome-dependent survival.
HnRNP L is important for the expression of oncogene SRSF3 and oncogenic potential of oral squamous cell carcinoma cells
Authors: Jia Rong , Zhang Si , Liu Miaomiao , Zhang Yan , Liu Yu , Fan Mingwen , Guo Jihua
Published: November 2016

Oral squamous cell carcinoma (OSCC) is the leading cause of death related to oral diseases. The mechanisms of OSCC development remain largely unknown. Heterogeneous nuclear ribonucleoprotein L (HnRNP L) is a multi-functional splicing factor. It has been reported to be an important regulator of apoptosis. However, the functions of hnRNP L in cancer need to be further explored. In the present study, we found that OSCC tissues expressed significantly higher levels of hnRNP L than normal tissues. Depletion of hnRNP L retarded cell growth, cell migration, and tumorigenesis of OSCC cells. HnRNP L regulates both the expression of oncogenic splicing factor SRSF3 and the alternative splicing of SRSF3 exon 4. Expression of hnRNP L is correlated with SRSF3 expression in OSCC tissues. These findings suggest that hnRNP L is important for the pathogenesis of OSCC and may be a novel potential therapeutic target of OSCC.
Bioinspired seeding of biomaterials using three dimensional microtissues induces chondrogenic stem cell differentiation and cartilage formation under growth factor free conditions
Authors: Leijten J. , Teixeira L. S. Moreira , Bolander J. , Ji W. , Vanspauwen B. , Lammertyn J. , Schrooten J. , Luyten F. P.
Published: November 2016

Cell laden biomaterials are archetypically seeded with individual cells and steered into the desired behavior using exogenous stimuli to control growth and differentiation. In contrast, direct cell-cell contact is instructive and even essential for natural tissue formation. Namely, microaggregation and condensation of mesenchymal progenitor cells triggers chondrogenesis and thereby drives limb formation. Yet a biomimetic strategy translating this approach into a cell laden biomaterial-based therapy has remained largely unexplored. Here, we integrate the microenvironment of cellular condensation into biomaterials by encapsulating microaggregates of a hundred human periosteum-derived stem cells. This resulted in decreased stemness-related markers, up regulation of chondrogenic genes and improved in vivo cartilage tissue formation, as compared to single cell seeded biomaterials. Importantly, even in the absence of exogenous growth factors, the microaggregate laden hydrogels outperformed conventional single cell laden hydrogels containing supraphysiological levels of the chondrogenic growth factor TGFB. Overall, the bioinspired seeding strategy described herein represents an efficient and growth factor-free approach to efficiently steer cell fate and drive tissue formation for biomaterial-based tissue engineering strategies.
Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies
Authors: Wu Nan , Song Yu-Long , Wang Bei , Zhang Xiang-Yang , Zhang Xu-Jie , Wang Ya-Li , Cheng Ying-Yin , Chen Dan-Dan , Xia Xiao-Qin , Lu Yi-Shan , Zhang Yong-An
Published: November 2016

The gut-associated lymphoid tissue, connected with liver via bile and blood, constructs a local immune environment of both defense and tolerance. The gut-liver immunity has been well-studied in mammals, yet in fish remains largely unknown, even though enteritis as well as liver and gallbladder syndrome emerged as a limitation in aquaculture. In this study, we performed integrative bioinformatic analysis for both transcriptomic (gut and liver) and proteomic (intestinal mucus and bile) data, in both healthy and infected tilapias. We found more categories of immune transcripts in gut than liver, as well as more adaptive immune in gut meanwhile more innate in liver. Interestingly reduced differential immune transcripts between gut and liver upon inflammation were also revealed. In addition, more immune proteins in bile than intestinal mucus were identified. And bile probably providing immune effectors to intestinal mucus upon inflammation was deduced. Specifically, many key immune transcripts in gut or liver as well as key immune proteins in mucus or bile were demonstrated. Accordingly, we proposed a hypothesized profile of fish gut-liver immunity, during either homeostasis or inflammation. Current data suggested that fish gut and liver may collaborate immunologically while keep homeostasis using own strategies, including potential unique mechanisms.
Hexacoordinated nitrogen(V) stabilized by high pressure
Authors: Kurzydłowski Dominik , Zaleski-Ejgierd Patryk
Published: November 2016

In all of its known connections nitrogen retains a valence shell electron count of eight therefore satisfying the golden rule of chemistry - the octet rule. Despite the diversity of nitrogen chemistry (with oxidation states ranging from + 5 to −3), and despite numerous efforts, compounds containing nitrogen with a higher electron count (hypervalent nitrogen) remain elusive and are yet to be synthesized. One possible route leading to nitrogen’s hypervalency is the formation of a chemical moiety containing pentavalent nitrogen atoms coordinated by more than four substituents. Here, we present theoretical evidence that a salt containing hexacoordinated nitrogen(V), in the form of an NF6− anion, could be synthesized at a modest pressure of 40 GPa (=400 kbar) via spontaneous oxidation of NF3 by F2. Our results indicate that the synthesis of a new class of compounds containing hypervalent nitrogen is within reach of current high-pressure experimental techniques.
Resonance states and beating pattern induced by quantum impurity scattering in Weyl/Dirac semimetals
Authors: Zheng Shi-Han , Wang Rui-Qiang , Zhong Min , Duan Hou-Jian
Published: November 2016

Currently, Weyl semimetals (WSMs) are drawing great interest as a new topological nontrivial phase. When most of the studies concentrated on the clean host WSMs, it is expected that the dirty WSM system would present rich physics due to the interplay between the WSM states and the impurities embedded inside these materials. We investigate theoretically the change of local density of states in three-dimensional Dirac and Weyl bulk states scattered off a quantum impurity. It is found that the quantum impurity scattering can create nodal resonance and Kondo peak/dip in the host bulk states, remarkably modifying the pristine spectrum structure. Moreover, the joint effect of the separation of Weyl nodes and the Friedel interference oscillation causes the unique battering feature. We in detail an- alyze the different contribution from the intra- and inter-node scattering processes and present various scenarios as a consequence of competition between them. Importantly, these behaviors are sensitive significantly to the displacement of Weyl nodes in energy or momentum, from which the distinctive fingerprints can be extracted to identify various semimetal materials experimentally by employing the scanning tunneling microscope.
High-efficient Synthesis of Graphene Oxide Based on Improved Hummers Method
Authors: Yu Huitao , Zhang Bangwen , Bulin Chaoke , Li Ruihong , Xing Ruiguang
Published: November 2016

As an important precursor and derivate of graphene, graphene oxide (GO) has received wide attention in recent years. However, the synthesis of GO in an economical and efficient way remains a great challenge. Here we reported an improved NaNO3-free Hummers method by partly replacing KMnO4 with K2FeO4 and controlling the amount of concentrated sulfuric acid. As compared to the existing NaNO3-free Hummers methods, this improved routine greatly reduces the reactant consumption while keeps a high yield. The obtained GO was characterized by various techniques, and its derived graphene aerogel was demonstrated as high-performance supercapacitor electrodes. This improved synthesis shows good prospects for scalable production and applications of GO and its derivatives.
Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count
Authors: Wada Yoshiko , Wada Kennosuke , Iwasaki Yuki , Kanaya Shigehiko , Ikemura Toshimichi
Published: November 2016

Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness.
SSA-ME Detection of cancer driver genes using mutual exclusivity by small subnetwork analysis
Authors: Pulido-Tamayo Sergio , Weytjens Bram , De Maeyer Dries , Marchal Kathleen
Published: November 2016

Because of its clonal evolution a tumor rarely contains multiple genomic alterations in the same pathway as disrupting the pathway by one gene often is sufficient to confer the complete fitness advantage. As a result, many cancer driver genes display mutual exclusivity across tumors. However, searching for mutually exclusive gene sets requires analyzing all possible combinations of genes, leading to a problem which is typically too computationally complex to be solved without a stringent a priori filtering, restricting the mutations included in the analysis. To overcome this problem, we present SSA-ME, a network-based method to detect cancer driver genes based on independently scoring small subnetworks for mutual exclusivity using a reinforced learning approach. Because of the algorithmic efficiency, no stringent upfront filtering is required. Analysis of TCGA cancer datasets illustrates the added value of SSA-ME: well-known recurrently mutated but also rarely mutated drivers are prioritized. We show that using mutual exclusivity to detect cancer driver genes is complementary to state-of-the-art approaches. This framework, in which a large number of small subnetworks are being analyzed in order to solve a computationally complex problem (SSA), can be generically applied to any problem in which local neighborhoods in a network hold useful information.
Anticipation of guilt for everyday moral transgressions: The role of the anterior insula and the influence of interpersonal psychopathic traits
Authors: Seara-Cardoso Ana , Sebastian Catherine L. , McCrory Eamon , Foulkes Lucy , Buon Marine , Roiser Jonathan P. , Viding Essi
Published: November 2016

Psychopathy is a personality disorder characterised by atypical moral behaviour likely rooted in atypical affective/motivational processing, as opposed to an inability to judge the wrongness of an action. Guilt is a moral emotion believed to play a crucial role in adherence to moral and social norms, but the mechanisms by which guilt (or lack thereof) may influence behaviour in individuals with high levels of psychopathic traits are unclear. We measured neural responses during the anticipation of guilt about committing potential everyday moral transgressions, and tested the extent to which these varied with psychopathic traits. We found a significant interaction between the degree to which anticipated guilt was modulated in the anterior insula and interpersonal psychopathic traits: anterior insula modulation of anticipated guilt was weaker in individuals with higher levels of these traits. Data from a second sample confirmed that this pattern of findings was specific to the modulation of anticipated guilt and not related to the perceived wrongness of the transgression. These results suggest a central role for the anterior insula in coding the anticipation of guilt regarding potential moral transgressions and advance our understanding of the neurocognitive mechanisms that may underlie propensity to antisocial behaviour.
Ethanol extract of Lophatheri Herba exhibits anti-cancer activity in human cancer cells by suppression of metastatic and angiogenic potential
Authors: Kim Aeyung , Im Minju , Gu Min Jung , Ma Jin Yeul
Published: November 2016

Lophatheri Herba (LH), dried leaf of Lophatherum gracile Brongn, has long been used to reduce thirst and treat fever and inflammation in Chinese medicine. Recent studies have shown that LH has anti-viral, anti-bacterial, anti-cancer, anti-oxidant, diuretic, and hyperglycemic properties. However, the effects of an ethanol extract of L. herba (ELH), at non-cytotoxic doses, on the metastatic and angiogenic abilities of malignant tumor cells have not been reported. We found that ELH significantly suppressed p38, JNK, and NF-κB activation and proteolytic activities under phorbol 12-myristate 13-acetate (PMA) stimulation, thus leading to a decrease in metastatic potential, including migration and invasion. In addition, ELH suppressed tumor-induced angiogenesis, including migration and tube formation in human umbilical vein endothelial cells (HUVECs) and microvessel sprouting from aortic rings via decreasing the pro-angiogenic factors in tumors. Interestingly, in ovo xenografts ELH-treated HT1080 cells did not increase in volume and eventually disappeared, owing to a lack of angiogenesis. Daily oral administration of ELH at 50 and 100 mg/kg markedly inhibited metastatic colonization of B16F10 cells in the lungs of C57BL/6J mice and caused no apparent side effects. These data collectively indicate that ELH is safe and may be useful for managing metastasis and growth of malignant cancers.
Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma
Authors: Nath Lekshmi R. , Gorantla Jaggaiah N. , Thulasidasan Arun Kumar T. , Vijayakurup Vinod , Shah Shabna , Anwer Shabna , Joseph Sophia M. , Antony Jayesh , Veena Kollery Suresh , Sundaram Sankar , Marelli Udaya K. , Lankalapalli Ravi S. , Anto Ruby John
Published: November 2016

We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin fromSolanum nigrumLinn, against liver cancer. The compound has been isolated and characterized from the leaves ofSolanum nigrumLinn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0.5 μM) than sorafenib (IC50: 5.8 μM), the only FDA-approved drug for liver cancer. Moreover, it induces cytotoxicity in all liver cancer cell lines, irrespective of their HBV status, while being non-toxic to normal immortalized hepatocytes. It induces apoptosis in HepG2 cells by down-regulating mainly the activation of MAPK and mTOR pathways. The drastic reduction in HepG2-xenograft tumor size achieved by uttroside B in NOD-SCID mice and substantiation of its biological safety through both acute and chronic toxicity studies in Swiss albino mice warrants clinical validation of the molecule against hepatic cancer, for which, the chemotherapeutic armamentarium currently has limited weapons.
N-acetyl ornithine deacetylase is a moonlighting protein and is involved in the adaptation of Entamoeba histolytica to nitrosative stress
Authors: Shahi Preeti , Trebicz-Geffen Meirav , Nagaraja Shruti , Hertz Rivka , Alterzon-Baumel Sharon , Methling Karen , Lalk Michael , Mazumder Mohit , Samudrala Gourinath , Ankri Serge
Published: November 2016

Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite’s survival in its host. In order to obtain insight into the mechanism of E. histolytica’s adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is detrimental to E. histolytica exposed to NS and that this detrimental effect is neutralized by NAOD or by a catalytically inactive NAOD (mNAOD). These results establish NAOD as a moonlighting protein, and highlight the unexpected role of this metabolic enzyme in the adaptation of the parasite to NS.
Dynamics of Disagreement: Large-Scale Temporal Network Analysis Reveals Negative Interactions in Online Collaboration
Authors: Tsvetkova Milena , García-Gavilanes Ruth , Yasseri Taha
Published: November 2016

Disagreement and conflict are a fact of social life. However, negative interactions are rarely explicitly declared and recorded and this makes them hard for scientists to study. In an attempt to understand the structural and temporal features of negative interactions in the community, we use complex network methods to analyze patterns in the timing and configuration of reverts of article edits to Wikipedia. We investigate how often and how fast pairs of reverts occur compared to a null model in order to control for patterns that are natural to the content production or are due to the internal rules of Wikipedia. Our results suggest that Wikipedia editors systematically revert the same person, revert back their reverter, and come to defend a reverted editor. We further relate these interactions to the status of the involved editors. Even though the individual reverts might not necessarily be negative social interactions, our analysis points to the existence of certain patterns of negative social dynamics within the community of editors. Some of these patterns have not been previously explored and carry implications for the knowledge collection practice conducted on Wikipedia. Our method can be applied to other large-scale temporal collaboration networks to identify the existence of negative social interactions and other social processes.
Genomic analysis reveals selection in Chinese native black pig
Authors: Fu Yuhua , Li Cencen , Tang Qianzi , Tian Shilin , Jin Long , Chen Jianhai , Li Mingzhou , Li Changchun
Published: November 2016

Identification of genomic signatures that help reveal mechanisms underlying desirable traits in domesticated pigs is of significant biological, agricultural and medical importance. To identify the genomic footprints left by selection during domestication of the Enshi black pig, a typical native and meat-lard breed in China, we generated about 72-fold coverage of the pig genome using pools of genomic DNA representing three different populations of Enshi black pigs from three different locations. Combining this data with the available whole genomes of 13 Chinese wild boars, we identified 417 protein-coding genes embedded in the selected regions of Enshi black pigs. These genes are mainly involved in developmental and metabolic processes, response to stimulus, and other biological processes. Signatures of selection were detected in genes involved in body size and immunity (RPS10 and VASN), lipid metabolism (GSK3), male fertility (INSL6) and developmental processes (TBX19). These findings provide a window into the potential genetic mechanism underlying development of desirable phenotypes in Enshi black pigs during domestication and subsequent artificial selection. Thus, our results illustrate how domestication has shaped patterns of genetic variation in Enshi black pigs and provide valuable genetic resources that enable effective use of pigs in agricultural production.
Timing and causes of North African wet phases during the last glacial period and implications for modern human migration
Authors: Hoffmann Dirk L. , Rogerson Mike , Spötl Christoph , Luetscher Marc , Vance Derek , Osborne Anne H. , Fello Nuri M. , Moseley Gina E.
Published: November 2016

We present the first speleothem-derived central North Africa rainfall record for the last glacial period. The record reveals three main wet periods at 65-61 ka, 52.5-50.5 ka and 37.5-33 ka that lead obliquity maxima and precession minima. We find additional minor wet episodes that are synchronous with Greenland interstadials. Our results demonstrate that sub-tropical hydrology is forced by both orbital cyclicity and North Atlantic moisture sources. The record shows that after the end of a Saharan wet phase around 70 ka ago, North Africa continued to intermittently receive substantially more rainfall than today, resulting in favourable environmental conditions for modern human expansion. The encounter and subsequent mixture of Neanderthals and modern humans – which, on genetic evidence, is considered to have occurred between 60 and 50 ka – occurred synchronously with the wet phase between 52.5 and 50.5 ka. Based on genetic evidence the dispersal of modern humans into Eurasia started less than 55 ka ago. This may have been initiated by dry conditions that prevailed in North Africa after 50.5 ka. The timing of a migration reversal of modern humans from Eurasia into North Africa is suggested to be coincident with the wet period between 37.5 and 33 ka.
Cascading and Parallelising Curvilinear Inertial Focusing Systems for High Volume, Wide Size Distribution, Separation and Concentration of Particles
Authors: Miller B. , Jimenez M. , Bridle H.
Published: November 2016

Inertial focusing is a microfluidic based separation and concentration technology that has expanded rapidly in the last few years. Throughput is high compared to other microfluidic approaches although sample volumes have typically remained in the millilitre range. Here we present a strategy for achieving rapid high volume processing with stacked and cascaded inertial focusing systems, allowing for separation and concentration of particles with a large size range, demonstrated here from 30 μm–300 μm. The system is based on curved channels, in a novel toroidal configuration and a stack of 20 devices has been shown to operate at 1 L/min. Recirculation allows for efficient removal of large particles whereas a cascading strategy enables sequential removal of particles down to a final stage where the target particle size can be concentrated. The demonstration of curved stacked channels operating in a cascaded manner allows for high throughput applications, potentially replacing filtration in applications such as environmental monitoring, industrial cleaning processes, biomedical and bioprocessing and many more.
ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer
Authors: Cedó Lídia , García-León Annabel , Baila-Rueda Lucía , Santos David , Grijalva Victor , Martínez-Cignoni Melanie Raquel , Carbó José M. , Metso Jari , López-Vilaró Laura , Zorzano Antonio , Valledor Annabel F. , Cenarro Ana , Jauhiainen Matti , Lerma Enrique , Fogelman Alan M. , Reddy Srinivasa T. , Escolà-Gil Joan Carles , Blanco-Vaca Francisco
Published: November 2016

Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.
mTORC1 inhibitor rapamycin and ER stressor tunicamycin induce differential patterns of ER-mitochondria coupling
Authors: Bravo-Sagua Roberto , López-Crisosto Camila , Parra Valentina , Rodriguez-Peña Marcelo , Rothermel Beverly A. , Quest Andrew F.G. , Lavandero Sergio
Published: November 2016

Efficient mitochondrial Ca2+ uptake takes place at contact points between the ER and mitochondria, and represents a key regulator of many cell functions. In a previous study with HeLa cells, we showed that ER-to-mitochondria Ca2+ transfer increases during the early phase of ER stress induced by tunicamycin as an adaptive response to stimulate mitochondrial bioenergetics. It remains unknown whether other types of stress signals trigger similar responses. Here we observed that rapamycin, which inhibits the nutrient-sensing complex mTORC1, increased ER-mitochondria coupling in HeLa cells to a similar extent as did tunicamycin. Interestingly, although global responses to both stressors were comparable, there were notable differences in the spatial distribution of such changes. While tunicamycin increased organelle proximity primarily in the perinuclear region, rapamycin increased organelle contacts throughout the entire cell. These differences were paralleled by dissimilar alterations in the distribution of regulatory proteins of the ER-mitochondria interface, heterogeneities in mitochondrial Ca2+ uptake, and the formation of domains within the mitochondrial network with varying mitochondrial transmembrane potential. Collectively, these data suggest that while increasing ER-mitochondria coupling appears to represent a general response to cell stress, the intracellular distribution of the associated responses needs to be tailored to meet specific cellular requirements.
Rotating lattice single crystal architecture on the surface of glass
Authors: Savytskii D. , Jain H. , Tamura N. , Dierolf V.
Published: November 2016

Defying the requirements of translational periodicity in 3D, rotation of the lattice orientation within an otherwise single crystal provides a new form of solid. Such rotating lattice single (RLS) crystals are found, but only as spherulitic grains too small for systematic characterization or practical application. Here we report a novel approach to fabricate RLS crystal lines and 2D layers of unlimited dimensions via a recently discovered solid-to-solid conversion process using a laser to heat a glass to its crystallization temperature but keeping it below the melting temperature. The proof-of-concept including key characteristics of RLS crystals is demonstrated using the example of Sb2S3 crystals within the Sb-S-I model glass system for which the rotation rate depends on the direction of laser scanning relative to the orientation of initially formed seed. Lattice rotation in this new mode of crystal growth occurs upon crystallization through a well-organized dislocation/disclination structure introduced at the glass/crystal interface. Implications of RLS growth on biomineralization and spherulitic crystal growth are noted.