bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic fungal protein-induced resistance and its effects on vegetable diseases
Authors: LIN T.-C. , LIN C.-L. , CHUNG W.-C. , CHUNG K.-R. , HUANG J.-W.
Published: March 2017

Plant defence systems can be induced by biotic and abiotic stress. Experiments were undertaken to explore the feasibility of different fungal proteins for the reduction of vegetable diseases. Total proteins purified from three soil-borne and five foliar fungal pathogens had no fungistatic effects nor did they trigger hypersensitive reactions on test plants. The abilities to promote plant growth and to reduce disease severity varied among test proteins and plants. Depending on test proteins, experiments have demonstrated that exogenous application of fungal proteins could reduce Alternaria brassicicola-induced black spot severity on cabbage, Colletotrichum spp.-induced anthracnose on Chinese cabbage and cucumber, Rhizoctonia solani-induced damping-off on sweet pepper and Chinese cabbage, and powdery mildew on cucumber seedlings. An Alternariaprotein effector 1 (Ape1)-coding gene was cloned from two Alternaria spp. and expressed in Escherichia coli. The expressed Ape1 reduced anthracnose incidence on cucumber leaves, indicating that Ape1 was the primary activator in the crude protein extracts responsible for disease reduction. Application of Alternaria proteins onto Chinese cabbage seedlings caused an increase of phenylalanine ammonia lyase and peroxidase activities in treated seedlings, which may have played a role in host defence.
‘If they don't use it, they lose it’: how organisational structures and practices shape residents’ physical movement in care home settings
Authors: HAWKINS REBECCA J. , PRASHAR ARVIN , LUSAMBILI ADELAIDE , ELLARD DAVID R. , GODFREY MARY
Published: March 2017

Older people living in long-term facilities (nursing and residential homes providing 24-hour care) spend the majority of their time inactive, despite the known health and wellbeing benefits of physical activity and reduced time spent sedentary. In order to successfully embed interventions that aim to increase physical activity or reduce sedentary behaviour, it is necessary to understand the features of the care environment that influence residents’ routine patterns of movement. Drawing on an organisational perspective, this paper explores the structures and mechanisms that shaped different care practices concerning residents’ movement in two contrasting care homes in the north of England. This study adopted an ethnographic approach, using a combination of qualitative observations, informal conversations and interviews. A grounded theory approach to data analysis was adopted. The findings illustrate the importance of translating espoused values of care into tangible and acceptable care practices, systems of management, staff training and development, and the use of care planning in residents’ routine patterns of movement. Understanding how organisational factors shape routine movement among care home residents will help inform the development of embedded and sustainable interventions that enhance physical activity and reduce sedentary behaviour. This study is part of a wider programme of research developing and testing a complex intervention, embedded within routine care, to reduce sedentary behaviour among care home residents.
GONE WITH THE EURO: A REAPPRAISAL OF THE PESETA’S ADJUSTMENT MECHANISM (1870-1998)
Authors: Serrano José María , Gadea María Dolores , Sabaté Marcela
Published: March 2017

The peseta was the Spanish currency for more than a century and, during this time, it played a remarkable role in adjusting the balance of payments. This paper presents a chronology of the moments when the adjustment was crucial, which, consistent with the macro-trilemma, coincided with periods of external openness. Moreover, this paper provides empirical support to the thesis that links the exceptionality of a floating peseta during the gold standard with fiscal profligacy.
Frequency of Ship Collisions in the Strait of Messina through Regulatory and Environmental Constraints Assessment
Authors: Cucinotta F. , Guglielmino E. , Sfravara F.
Published: March 2017

The Strait of Messina is a very busy sea area that separates Sicily and the Italian mainland. In respect of environment and for the prevention of human loss, it is fundamental to have an estimate of the possible ship accidents that could occur. In this work, the approach used is the International Association of Lighthouse Authorities Waterways Risk Assessment Program (IWRAP) model. The first part of the paper describes the local and global traffic and the separation scheme in the Strait of Messina. The model input data is obtained from the Vessel Traffic Service (VTS) system thanks to the Coast Guard of Messina. The second part concerns calculation of the geometrical collisions (number of collisions in different scenarios) and the causation probability. This analysis is the basis for the discussion of new regulatory constraints due to the future realisation of new piers in the south and the planned unification of the two Port Authorities of the two shores into one single authority.
Synthetic Biology between Self-Regulation and Public Discourse: Ethical Issues and the Many Roles of the Ethicist
Authors: ARNASON GARDAR
Published: March 2017

This article discusses the roles of ethicists in the governance of synthetic biology. I am particularly concerned with the idea of self-regulation of bioscience and its relationship to public discourse about ethical issues in bioscience. I will look at the role of philosophical ethicists at different levels and loci, from the “embedded ethicist” in the laboratory or research project, to ethicists’ impact on policy and public discourse. In a democratic society, the development of governance frameworks for emerging technologies, such as synthetic biology, needs to be guided by a well-informed public discourse. In the case of synthetic biology, the public discourse has to go further than merely considering technical issues of biosafety and biosecurity, or risk management, to consider more philosophical issues concerning the meaning and value of “life” between the natural and the synthetic. I argue that ethicists have moral expertise to bring to the public arena, which consists not only in guiding the debate but also in evaluating arguments and moral positions and making normative judgments. When ethicists make normative claims or moral judgments, they must be transparent about their theoretical positions and basic moral standpoints.
Synthetic Biology: The Response of the Commission of the (Catholic) Bishops’ Conferences of the European Community
Authors: HEAVEY PATRICK
Published: March 2017

The Commission of the (Catholic) Bishops’ Conferences of the European Community (COMECE) has issued an opinion on the ethics of synthetic biology (synbio). Examining synbio from religious and more general ethical perspectives, it examines synbio’s potential pros and cons, as well as whether it is ethical in and of itself. Its conclusions mirror those of the ethical mainstream; namely, that synbio may present humanity with opportunities for both great advancement and great destruction. It suggests a prudent approach, and calls for regulation to be used to encourage positive outcomes while reducing the likelihood of negative ones.
Snubbing Seth Rogen: Does Celebrity Testimony Increase Congressional Hearing Attendance?
Authors: Atkinson Matthew D. , DeWitt Darin
Published: March 2017

Academic and popular accounts hold that celebrity activists command the attention of political elites. One manifestation of this idea is that celebrities garner greater congressional attention at committee hearings than the substantive experts who typically serve as witnesses. This implies that Members of Congress do not value interaction with experts and are willing to forego those interactions to allocate time to activities with low opportunity costs—activities unimportant enough that they can be passed up for a celebrity encounter. To evaluate these claims, we examined hearing attendance during a 20-year period. We found that celebrity witnesses have little effect on member attendance rates, which suggests that celebrities are a less efficacious route to congressional attention than is commonly believed.
Gender in the Journals: Publication Patterns in Political Science
Authors: Teele Dawn Langan , Thelen Kathleen
Published: March 2017

This article explores publication patterns across 10 prominent political science journals, documenting a significant gender gap in publication rates for men and women. We present three broad findings. First, we find no evidence that the low percentage of female authors simply mirrors an overall low share of women in the profession. Instead, we find continued underrepresentation of women in many of the discipline’s top journals. Second, we find that women are not benefiting equally in a broad trend across the discipline toward coauthorship. Most published collaborative research in these journals emerges from all-male teams. Third, it appears that the methodological proclivities of the top journals do not fully reflect the kind of work that female scholars are more likely than men to publish in these journals. The underrepresentation of qualitative work in many journals is associated as well with an underrepresentation of female authors.
The UCD Population of the Coma Cluster
Authors: Chiboucas Kristin , Ferguson Peter , Tully R. Brent , Carter David , Phillipps Steven , Peng Eric
Published: March 2017

UCDs are super massive star clusters found largely in dense regions but have also been found around individual galaxies and in smaller groups. Their origin is still under debate but consensus is that they formed either during major galaxy mergers as mergers of super massive star clusters, are simply the high mass end of the globular cluster luminosity function and formed in the same way as globular clusters, or that they formed from the threshing of galaxies and are remnant nuclear star clusters, which themselves may have formed from the mergers of globular star clusters within galaxies. We are attempting to disentangle these competing formation scenarios with a large survey of UCDs in the Coma cluster. Using ACS two-passband imaging from the HST/ACS Coma Cluster Treasury Survey, we are using colors and sizes to identify the UCD cluster members. With a large sample within the core region of the Coma cluster, we will use the population size, properties, and spatial distribution, and comparison with the Coma globular cluster and nuclear star cluster populations to discriminate between the threshing and globular cluster scenarios. In particular, previously we have found a possible correlation of UCD colors with host galaxy and a possible excess of UCDs around a non-central giant galaxy with an unusually large globular cluster population, both suggestive of a globular cluster origin. With a larger sample size, we are investigating whether the color correlation with host persists and whether the UCD population is consistent with, or in excess of, the bright end of the GCLF. We present initial results from the survey.
From a star cluster ensemble to its formation history
Authors: Schulz Christine , Hilker Michael
Published: March 2017

The present-day sample of ultra-compact dwarf galaxies (UCDs) and globular clusters (GCs) around NGC 1399 is interpreted to be composed of individual star cluster (SC) populations. It is assumed that such an SC population forms at a constant star-formation rate (SFR), and its mass distribution is described by the embedded cluster mass function (ECMF) up to the upper limit Mmax. The GCs and UCDs probably formed in interactions of the progenitor galaxies during the assembly of the central Fornax galaxy cluster which is why we use them as tracers of those events. After some corrections, the overall GC/UCD mass function is decomposed into separate SC populations, each described by an ECMF. Mmax of each ECMF is converted to an SFR according to the SFR-Mmax relation, revealing the SFRs reached during the assembly of galaxies in the central Fornax galaxy cluster.
CHaMP: From Molecular Clouds to Massive Young Clusters
Authors: Barnes Peter J.
Published: March 2017

I review the major science outcomes to date of the Galactic Census of High- and Medium-mass Protostars (CHaMP), and also report the latest observational results on this unbiased, uniform sample of massive, cluster-forming molecular clumps, based on new mm-wave and IR data. These clouds represent the vast, subthermally-excited population of clumps predicted by Narayanan et al. (2008) to dominate the molecular mass of disk galaxies. Besides confirming their existence, we have presented evidence that these massive clumps probably spend a large fraction (90–95%) of their long lives (possibly up to 100 Myr) in a mostly quiescent, low star formation rate (SFR) state. This is likely ended when a density or internal pressure threshold is crossed, after which vigorous, massive cluster formation consumes the densest gas with a high SFR, dispersing the embedding envelope. New results presented in two other posters at this Symposium include (1) the first analysis of HCN emission from the dense gas (Schap et al.2015), and (2) the first deep photometry of clusters in this sample based on NIR AAT & CTIO data, and on MIR Warm Spitzer IRAC data (Dallilar et al.2015).
Dynamical Evolution of Outer-Halo Globular Clusters
Authors: Küpper Andreas H. W. , Zonoozi Akram H. , Haghi Hosein , Lützgendorf Nora , Mieske Steffen , Frank Matthias , Baumgardt Holger , Kroupa Pavel
Published: March 2017

Outer-halo globular clusters show large half-light radii and flat stellar mass functions, depleted in low-mass stars. Using N-body simulations of globular clusters on eccentric orbits within a Milky Way-like potential, we show how a cluster’s half-mass radius and its mass function develop over time. The slope of the central mass function flattens proportionally to the amount of mass a cluster has lost, and the half-mass radius grows to a size proportional to the average strength of the tidal field. The main driver of these processes is mass segregation of dark remnants. We conclude that the extended, depleted clusters observed in the Milky Way must have had small half-mass radii in the past, and that they expanded due to the weak tidal field they spend most of their lifetime in. Moreover, their mass functions must have been steeper in the past but flattened significantly as a cause of mass segregation and tidal mass loss.
The HST survey of Magellanic-Cloud clusters and of their stellar populations
Authors: Milone A. P.
Published: March 2017

A large number of intermediate-age (~1-2-Gyr old) globular clusters (GCs) in the Large and the Small Magellanic Cloud (MC) exhibit either bimodal or extended main-sequence (MS) turn off and dual red clump (RC). Moreover, recent papers have shown that the MS of the young clusters NGC 1844 and NGC 1856 is either broadened or split. These features of the color-magnitude diagram (CMD) are not consistent with a single isochrone and suggest that star clusters in MCs have experienced a prolonged star formation, in close analogy with Milky-Way GCs with multiple stellar populations. As an alternative, stellar rotation or interacting binaries can be responsible of the CMD morphology. In the following I will summarize the observational scenario and provide constraints on the nature of the complex CMD of young and intermediate-age MC clusters from our ongoing photometric survey with the Hubble Space Telescope (HST).
Mapping out the origins of compact stellar systems
Authors: Romanowsky Aaron J. , Brodie Jean P. ,   the SAGES
Published: March 2017

We present a suite of extragalactic explorations of the origins and nature of globular clusters (GCs) and ultra-compact dwarfs (UCDs), and the connections between them. An example of GC metallicity bimodality is shown to reflect underlying, distinct metal-poor and metal-rich stellar halo populations. Metallicity-matching methods are used to trace the birth sites and epochs of GCs in giant E/S0s, pointing to clumpy disk galaxies at z ~ 3 for the metal-rich GCs, and to a combination of accreted and in-situ formation modes at z ~ 5–6 for the metal-poor GCs. An increasingly diverse zoo of compact stellar systems is being discovered, including objects that bridge the gaps between UCDs and faint fuzzies, and between UCDs and compact ellipticals. Many of these have properties pointing to origins as the stripped nuclei of larger galaxies, and a smoking-gun example is presented of an ω Cen-like star cluster embedded in a tidal stream.
Exploring the UV excess in star clusters of different mass
Authors: Hernández-Pérez Fabiola , Bruzual Gustavo , Gladis Magris C.
Published: March 2017

We compute the expected spectral energy distribution of stellar populations of mass characteristic of star clusters taking into account stochastic fluctuations in the number of stars populating the IMF, and the presence of interacting binary stars in the cluster population. We evaluate under what circumstances the UV excess phenomenon is expected to appear in star clusters of different mass, and which is its most likely source: the stochastic fluctuations, the result of binary interactions, or a mixture of both.
Clusters of high-mass protostars: From extreme clouds to mini-bursts of star formation
Authors: Motte Frédérique , Louvet Fabien , Nguyễn Lu'o'ng Quang
Published: March 2017

Herschel revealed high-density cloud filaments of several pc3, which are forming clusters of OB-type stars. Counting Herschel protostars gives a direct measure of the mass of stars forming in a period of ~105 yrs, the “instantaneous” star formation activity. Given their activity, these so-called mini-starburst cloud ridges could be seen as “miniature and instant models” of starburst galaxies. Their characteristics could shed light on the origin of massive clusters.
Fundamental Properties of a Large, Unbiased Sample of Massive, Young, Embedded Star Clusters in the Milky Way
Authors: Dallilar Yigit , Barnes Peter , Lada Elizabeth , Ryder Stuart
Published: March 2017

In this project, we focus on the analysis of infrared observations of the clumps defined with the Galactic Census of High- and Medium-mass Protostars (ChaMP) (Barneset al.2011). We derive line of sight infrared extinction values, star counts and protostar candidates around the molecular gas emission obtained with the Mopra telescope. Then, we examine the correlation between radio and infrared properties of the clumps. For this stage of the project, we use the Vela-Carina and 2MASS catalogs to obtain a preliminary understanding of the final results. For the later stages, we will extract infrared photometry from our deep AAT near-IR andSpitzer3.6 and 4.5 μm images. With the final deep photometry results, we will compile the properties of individual clusters.
Targeting the pro‐inflammatory factor CCL2 (MCP‐1) with Bindarit for influenza A (H7N9) treatment
Authors: Wolf Stefan , Johnson Scott , Perwitasari Olivia , Mahalingam Suresh , Tripp Ralph A
Published: March 2017

Influenza A viruses are important human and animal pathogens. Seasonal influenza viruses cause infections every year, and occasionally zoonotic viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. Three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus were reported in 2013, and there have been several cases reported across South East Asia, and recently in North America. Most patients experience severe respiratory illness, with mortality rates approaching 40%. No vaccine is currently available and the use of antivirals is complicated due to the emergence of drug resistant strains. Thus, there is a need to identify new drugs for therapeutic intervention and disease control. In humans, following H7N9 infection, there is excessive expression of pro‐inflammatory factors CCL2, IL‐6, IL‐8, IFNα, interferon‐γ, IP‐10, MIG and macrophage inflammatory protein‐1β, which has been shown to contribute to fatal disease outcomes in mouse models of infection. In the current study, the potent inhibitor of CCL2 synthesis, Bindarit, was examined as a countermeasure for H7N9‐induced inflammation in a mouse model. Bindarit treatment of mice did not have any substantial therapeutic efficacy in H7N9 infection. Consequently, the results suggest that Bindarit may be ill‐advised in the treatment of influenza H7N9 infection.
Chirality in microbial biofilms is mediated by close interactions between the cell surface and the substratum
Authors: Jauffred Liselotte , Munk Vejborg Rebecca , Korolev Kirill S , Brown Stanley , Oddershede Lene B
Published: March 2017

From microbial biofilms to human migrations, spatial competition is central to the evolutionary history of many species. The boundary between expanding populations is the focal point of competition for space and resources and is of particular interest in ecology. For all Escherichia coli strains studied here, these boundaries move in a counterclockwise direction even when the competing strains have the same fitness. We find that chiral growth of bacterial colonies is strongly suppressed by the expression of extracellular features such as adhesive structures and pili. Experiments with other microbial species show that chiral growth is found in other bacteria and exclude cell wall biosynthesis and anisotropic shape as the primary causes of chirality. Instead, intimate contact with the substratum is necessary for chirality. Our results demonstrate that through a handful of surface molecules cells can fundamentally reorganize their migration patterns, which might affect intra- and interspecific competitions through colony morphology or other mechanisms.
Prokaryote genome fluidity is dependent on effective population size
Authors: Andreani Nadia Andrea , Hesse Elze , Vos Michiel
Published: March 2017

Many prokaryote species are known to have fluid genomes, with different strains varying markedly in accessory gene content through the combined action of gene loss, gene gain via lateral transfer, as well as gene duplication. However, the evolutionary forces determining genome fluidity are not yet well understood. We here for the first time systematically analyse the degree to which this distinctive genomic feature differs between bacterial species. We find that genome fluidity is positively correlated with synonymous nucleotide diversity of the core genome, a measure of effective population size Ne. No effects of genome size, phylogeny or homologous recombination rate on genome fluidity were found. Our findings are consistent with a scenario where accessory gene content turnover is for a large part dictated by neutral evolution.
PABPN1 gene therapy for oculopharyngeal muscular dystrophy
Authors: Malerba A. , Klein P. , Bachtarzi H. , Jarmin S. A. , Cordova G. , Ferry A. , Strings V. , Espinoza M. Polay , Mamchaoui K. , Blumen S. C. , St Guily J. Lacau , Mouly V. , Graham M. , Butler-Browne G. , Suhy D. A. , Trollet C. , Dickson G.
Published: March 2017

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment.
Role for formin-like 1-dependent acto-myosin assembly in lipid droplet dynamics and lipid storage
Authors: Pfisterer Simon G. , Gateva Gergana , Horvath Peter , Pirhonen Juho , Salo Veijo T. , Karhinen Leena , Varjosalo Markku , Ryhänen Samppa J. , Lappalainen Pekka , Ikonen Elina
Published: March 2017

Lipid droplets (LDs) are cellular organelles specialized in triacylglycerol (TG) storage undergoing homotypic clustering and fusion. In non-adipocytic cells with numerous LDs this is balanced by poorly understood droplet dissociation mechanisms. We identify non-muscle myosin IIa (NMIIa/MYH-9) and formin-like 1 (FMNL1) in the LD proteome. NMIIa and actin filaments concentrate around LDs, and form transient foci between dissociating LDs. NMIIa depletion results in decreased LD dissociations, enlarged LDs, decreased hydrolysis and increased storage of TGs. FMNL1 is required for actin assembly on LDs in vitro and for NMIIa recruitment to LDs in cells. We propose a novel acto-myosin structure regulating lipid storage: FMNL1-dependent assembly of myosin II-functionalized actin filaments on LDs facilitates their dissociation, thereby affecting LD surface-to-volume ratio and enzyme accessibility to TGs. In neutrophilic leucocytes from MYH9-related disease patients NMIIa inclusions are accompanied by increased lipid storage in droplets, suggesting that NMIIa dysfunction may contribute to lipid imbalance in man.
Rapid electron transfer by the carbon matrix in natural pyrogenic carbon
Authors: Sun Tianran , Levin Barnaby D. A. , Guzman Juan J. L. , Enders Akio , Muller David A. , Angenent Largus T. , Lehmann Johannes
Published: March 2017

Surface functional groups constitute major electroactive components in pyrogenic carbon. However, the electrochemical properties of pyrogenic carbon matrices and the kinetic preference of functional groups or carbon matrices for electron transfer remain unknown. Here we show that environmentally relevant pyrogenic carbon with average H/C and O/C ratios of less than 0.35 and 0.09 can directly transfer electrons more than three times faster than the charging and discharging cycles of surface functional groups and have a 1.5 V potential range for biogeochemical reactions that invoke electron transfer processes. Surface functional groups contribute to the overall electron flux of pyrogenic carbon to a lesser extent with greater pyrolysis temperature due to lower charging and discharging capacities, although the charging and discharging kinetics remain unchanged. This study could spur the development of a new generation of biogeochemical electron flux models that focus on the bacteria–carbon–mineral conductive network.
TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
Authors: Thiele Nina D. , Wirth Jan W. , Steins David , Koop Anja C. , Ittrich Harald , Lohse Ansgar W. , Kluwe Johannes
Published: March 2017

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is upregulated during hepatic fibrogenesis and considered to promote fibrosis in the injured liver by inhibition of matrix metalloproteases (MMP) and degradation of extracellular matrix. Moreover, TIMP-1 displays anti-apoptotic properties, in patients with hepatocellular carcinoma (HCC) TIMP-1 serum levels are elevated and high TIMP-1 expression levels in HCC are associated with a poor prognosis. Therefore, TIMP-1 could functionally link fibrogenesis and carcinogenesis in the liver. The aim of our study was to characterize the role of TIMP-1 in hepatic fibrogenesis and carcinogenesis. Experimental hepatic fibrogenesis as well as diethylnitrosamine (DEN) -induced hepatocarcinogenesis were studied in TIMP-1-deficient mice and wild type littermates. Hepatic TIMP-1 expression was upregulated following induction of liver fibrosis by bile duct ligation (BDL) or by carbon tetrachloride (CCl4). Unexpectedly, in comparison to wild type littermates, TIMP-1-deficient mice were not protected from liver fibrosis induced by BDL or CCl4. TIMP-1 expression was significantly higher in HCC nodules than in surrounding liver tissue. However, experimental hepatic carcinogenesis was similar in TIMP-1-deficient mice and wild type littermates following DEN-treatment or combined treatment with DEN and CCl4. Therefore we concluded that TIMP-1 is not essential for hepatic fibrogenesis and carcinogenesis in mice.
Identification of leader and self-organizing communities in complex networks
Authors: Fu Jingcheng , Zhang Weixiong , Wu Jianliang
Published: March 2017

Community or module structure is a natural property of complex networks. Leader communities and self-organizing communities have been introduced recently to characterize networks and understand how communities arise in complex networks. However, identification of leader and self-organizing communities is technically challenging since no adequate quantification has been developed to properly separate the two types of communities. We introduced a new measure, called ratio of node degree variances, to distinguish leader communities from self-organizing communities, and developed a statistical model to quantitatively characterize the two types of communities. We experimentally studied the power and robustness of the new method on several real-world networks in combination of some of the existing community identification methods. Our results revealed that social networks and citation networks contain more leader communities whereas technological networks such as power grid network have more self-organizing communities. Moreover, our results also indicated that self-organizing communities tend to be smaller than leader communities. The results shed new lights on community formation and module structures in complex systems.
Diffuse lesion and necrosis tied to poorer prognosis of interdigitating dendritic cell sarcoma: cases report and a pooled analysis
Authors: Shi Feng , Song Qingkun , Wang Lingling , Gao Ying , Chang Hong
Published: March 2017

Interdigitating dendritic cell sarcoma is a neoplastic proliferation of interdigitating dendritic cells and no therapeutic consensus exists. This study aimed to investigate the prognostic impacts of tumor lesion, cellular atypia, mitosis and necrosis on the interdigitating dendritic cell sarcoma. Case reports and pooled analyses were designed to explore the relationships. One case was a 40-years old man with localized lesion, moderate to notable cellular atypia, 30 mitoses per 10 high-power fields and no necrosis and the progression-free survival was longer than 20 months. The other case was a 62-years old woman with diffuse lesion, notable cellular atypia, less than one mitosis per 10 high-power fields and diffuse necrosis and the progression-free survival was shorter than 1 month. Cellular atypia and mitosis had not any relationship with survival. Compared with localized lesion, diffuse lesion presented a 2.92-fold risk of progression (HR = 2.92, 95% CI 1.01, 8.51) and an 8.79-fold risk of death (HR = 8.79, 95% CI 1.86, 41.64). Diffuse necrosis presented a 4.39-fold higher progression risk (HR = 5.39, 95% CI 1.78, 16.29) and a 5.37-fold higher death risk (HR = 6.37, 95% CI 1.46, 27.86) than focal or no necrosis. Diffuse lesion and diffuse necrosis were indicators of poorer prognosis and the clinical application should be warranted in further studies.
Computer vision distortion correction of scanning probe microscopy images
Authors: Gaponenko Iaroslav , Tückmantel Philippe , Ziegler Benedikt , Rapin Guillaume , Chhikara Manisha , Paruch Patrycja
Published: March 2017

Since its inception, scanning probe microscopy (SPM) has established itself as the tool of choice for probing surfaces and functionalities at the nanoscale. Although recent developments in the instrumentation have greatly improved the metrological aspects of SPM, it is still plagued by the drifts and nonlinearities of the piezoelectric actuators underlying the precise nanoscale motion. In this work, we present an innovative computer-vision-based distortion correction algorithm for offline processing of functional SPM measurements, allowing two images to be directly overlaid with minimal error – thus correlating position with time evolution and local functionality. To demonstrate its versatility, the algorithm is applied to two very different systems. First, we show the tracking of polarisation switching in an epitaxial Pb(Zr0.2Ti0.8)O3 thin film during high-speed continuous scanning under applied tip bias. Thanks to the precise time-location-polarisation correlation we can extract the regions of domain nucleation and track the motion of domain walls until the merging of the latter in avalanche-like events. Secondly, the morphology of surface folds and wrinkles in graphene deposited on a PET substrate is probed as a function of applied strain, allowing the relaxation of individual wrinkles to be tracked.
Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
Authors: Olivares A. M. , Jelcick A. S. , Reinecke J. , Leehy B. , Haider A. , Morrison M. A. , Cheng L. , Chen D. F. , DeAngelis M. M. , Haider N. B.
Published: March 2017

Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD). The mouse models lack key NHRS (Nr2e3, RORA) or epigenetic (Ezh2) factors. Fifty-four total miRNAs were differentially expressed, potentially targeting over 150 genes in 18 major representative networks including angiogenesis, metabolism, and immunity. We identified sixty-eight genes and 5 miRNAS directly regulated by NR2E3 and/or RORA. After a comprehensive analysis, we discovered multimodal regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD. These studies provide insight into the complex, dynamic modulation of gene networks as well as their impact on human disease, and provide novel data for the development of innovative and more effective therapeutics.
Neuronal p38α mediates synaptic and cognitive dysfunction in an Alzheimer’s mouse model by controlling β-amyloid production
Authors: Colié Sandra , Sarroca Sara , Palenzuela Rocío , Garcia Idoia , Matheu Ander , Corpas Rubén , Dotti Carlos G. , Esteban José A. , Sanfeliu Coral , Nebreda Angel R.
Published: March 2017

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a severe and progressive neuronal loss leading to cognitive dysfunctions. Previous reports, based on the use of chemical inhibitors, have connected the stress kinase p38α to neuroinflammation, neuronal death and synaptic dysfunction. To explore the specific role of neuronal p38α signalling in the appearance of pathological symptoms, we have generated mice that combine expression of the 5XFAD transgenes to induce AD symptoms with the downregulation of p38α only in neurons (5XFAD/p38α∆-N). We found that the neuronal-specific deletion of p38α improves the memory loss and long-term potentiation impairment induced by 5XFAD transgenes. Furthermore, 5XFAD/p38α∆-N mice display reduced amyloid-β accumulation, improved neurogenesis, and important changes in brain cytokine expression compared with 5XFAD mice. Our results implicate neuronal p38α signalling in the synaptic plasticity dysfunction and memory impairment observed in 5XFAD mice, by regulating both amyloid-β deposition in the brain and the relay of this accumulation to mount an inflammatory response, which leads to the cognitive deficits.
Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection
Authors: Wassmer Sarah J. , Carvalho Livia S. , György Bence , Vandenberghe Luk H. , Maguire Casey A.
Published: March 2017

Widespread gene transfer to the retina is challenging as it requires vector systems to overcome physical and biochemical barriers to enter and diffuse throughout retinal tissue. We investigated whether exosome-associated adeno-associated virus, (exo-AAV) enabled broad retinal targeting following intravitreal (IVT) injection, as exosomes have been shown to traverse biological barriers and mediate widespread distribution upon systemic injection. We packaged an AAV genome encoding green fluorescent protein (GFP) into conventional AAV2 and exo-AAV2 vectors. Vectors were IVT injected into the eyes of adult mice. GFP expression was noninvasively monitored by fundus imaging and retinal expression was analyzed 4 weeks post-injection by qRT-PCR and histology. Exo-AAV2 outperformed conventional AAV2 in GFP expression based on fundus image analysis and qRT-PCR. Exo-AAV2 demonstrated deeper penetration in the retina, efficiently reaching the inner nuclear and outer plexiform, and to a lesser extent the outer nuclear layer. Cell targets were ganglion cells, bipolar cells, Müller cells, and photoreceptors. Exo-AAV2 serves as a robust gene delivery tool for murine retina, and the simplicity of production and isolation should make it widely applicable to basic research of the eye.
A novel method for non-destructive determination of hair photo-induced damage based on multispectral imaging technology
Authors: Cao Yue , Qu Hao , Xiong Can , Liu Changhong , Zheng Lei
Published: March 2017

Extended exposure to sunlight may give rise to chemical and physical damages of human hairs. In this work, we report a novel method for non-destructive quantification of hair photodamage via multispectral imaging (MSI) technology. We show that the multispectral reflectance value in near-infrared region has a strong correlation with hair photodamage. More specifically, the hair segments with longer growing time and the same hair root segment after continuous ultraviolet (UV) irradiation displaying more severe photodamage observed via scanning electron microscopy (SEM) micrographs showed significantly higher multispectral reflectance value. Besides, the multispectral reflectance value of hair segments with different growing time was precisely reproduced by exposing the same hair root segment to specific durations of UV irradiation, suggesting that MSI can be adequately applied to determine the sunlight exposure time of the hair. The loss of cystine content of photodamaged hairs was identified to be the main factor that physiologically contributed to the morphological changes of hair surface fibers and hence the variation of their multispectral reflectance spectra. Considering the environmental information recording nature of hairs, we believe that MSI for non-destructive evaluation of hair photodamage would prove valuable for assessing sunlight exposure time of a subject in the biomedical fields.
PCTK3/CDK18 regulates cell migration and adhesion by negatively modulating FAK activity
Authors: Matsuda Shinya , Kawamoto Kohei , Miyamoto Kenji , Tsuji Akihiko , Yuasa Keizo
Published: March 2017

PCTAIRE kinase 3 (PCTK3) is a member of the cyclin dependent kinase family, but its physiological function remains unknown. We previously reported that PCTK3-knockdown HEK293T cells showed actin accumulation at the leading edge, suggesting that PCTK3 is involved in the regulation of actin reorganization. In this study, we investigated the physiological function and downstream signal transduction molecules of PCTK3. PCTK3 knockdown in HEK293T cells increased cell motility and RhoA/Rho-associated kinase activity as compared with control cells. We also found that phosphorylation at residue Tyr-397 in focal adhesion kinase (FAK) was increased in PCTK3-knockdown cells. FAK phosphorylation at Tyr-397 was increased in response to fibronectin stimulation, whereas its phosphorylation was suppressed by PCTK3. In addition, excessive expression of PCTK3 led to the formation of filopodia during the early stages of cell adhesion in HeLa cells. These results indicate that PCTK3 controls actin cytoskeleton dynamics by negatively regulating the FAK/Rho signaling pathway.
An Inter-comparison of Three Heat Wave Types in China during 1961–2010: Observed Basic Features and Linear Trends
Authors: Chen Yang , Li Yi
Published: March 2017

Using observed daily temperatures in China, three independent types of heat waves (HWs), including daytime HWs, nighttime HWs, and compound HWs (with both extreme daily maxima and minima), were defined. Different types of HWs showed distinctive preferences in occurrence locations and timing. However, spatial patterns of accompanying relative humidity were generally independent of categorization, except for closer association of nighttime events with high humidity level. Compound HWs and nighttime HWs experienced significant increases in frequency, participating days, mean duration, intensity and areal extent. Conversely, significant decreasing trends of above indicators prevailed in daytime HWs, especially in central-eastern China. Tendency of relative humidity changes didn’t vary with HW types. Instead it caused an interesting phenomenon that dry HWs in the west became more humid and humid events in the east got dryer, as manifested most obviously in compound type. Thorough comparisons highlight the evolutionary dominance of HW types. Specifically, previously-dominating independent daytime HWs have been increasingly replaced by independent nighttime events in central-eastern China, and by compound HWs in southern China. That’s the very reason for negative trends of independent daytime HWs in eastern China, even in a warming climate.
Microvascular vasodilator properties of the angiotensin II type 2 receptor in a mouse model of type 1 diabetes
Authors: Begorre Marc-Antoine , Dib Abdallah , Habchi Khalil , Guihot Anne-Laure , Bourreau Jennifer , Vessieres Emilie , Blondeau Bertrand , Loufrani Laurent , Chabbert Marie , Henrion Daniel , Fassot Céline
Published: March 2017

Diabetes Mellitus is associated with severe cardiovascular disorders involving the renin-angiotensin system, mainly through activation of the angiotensin II type 1 receptor (AT1R). Although the type 2 receptor (AT2R) opposes the effects of AT1R, with vasodilator and anti-trophic properties, its role in diabetes is debatable. Thus we investigated AT2R-mediated dilatation in a model of type 1 diabetes induced by streptozotocin in 5-month-old male mice lacking AT2R (AT2R−/y). Glucose tolerance was reduced and markers of inflammation and oxidative stress (cyclooxygenase-2, gp91phox p22phox and p67phox) were increased in AT2R−/y mice compared to wild-type (WT) animals. Streptozotocin-induced hyperglycaemia was higher in AT2R−/y than in WT mice. Arterial gp91phox and MnSOD expression levels in addition to blood 8-isoprostane and creatinine were further increased in diabetic AT2R−/y mice compared to diabetic WT mice. AT2R-dependent dilatation in both isolated mesenteric resistance arteries and perfused kidneys was greater in diabetic mice than in non-diabetic animals. Thus, in type 1 diabetes, AT2R may reduce glycaemia and display anti-oxidant and/or anti-inflammatory properties in association with greater vasodilatation in mesenteric arteries and in the renal vasculature, a major target of diabetes. Therefore AT2R might represent a new therapeutic target in diabetes.
Endoscopic nipple sparing mastectomy with immediate implant-based reconstruction versus breast conserving surgery: a long-term study
Authors: Du Junze , Liang Quankun , Qi Xiaowei , Ming Jia , Liu Jing , Zhong Ling , Fan Linjun , Jiang Jun
Published: March 2017

To evaluate the differences between endoscopic nipple sparing mastectomy (ENSM) with immediate implant-based reconstruction and breast conserving surgery(BCS) applied to early-stage breast cancer in postoperative outcomes, function, and cosmesis. we made a prospective, non-randomized study reviewed a total of 346 cases of breast cancer from January 2007 to December 2011, including 189 cases of BCS and 157 cases of ENSM. All the patients were followed up to April 2016, with a median follow-up time of 74 months. The operative time, blood loss and drainage, postoperative complications, postoperative cosmesis, local recurrence rate, disease-free survival rate and overall survival rate of the two groups were compared. we found out that the operative time of ENSM was longer than that of BCS. There was no difference in blood loss and drainage, the postoperative complications, the disease-free survival rate and overall survival rate between the two groups. In regarding to cosmesis, patients in the ENSM group were more likely to get a satisfactory postoperative breast appearance. we reached a conclusion that ENSM is a safe and effective operative method retainingadvantages of TSSM to further improve the postoperative cosmetic effect, without increasing other risks. The surgery provides a new choice for patients with early-stage breast cancer.
Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types
Authors: Chen Ying-Jiun J. , Friedman Brad A. , Ha Connie , Durinck Steffen , Liu Jinfeng , Rubenstein John L. , Seshagiri Somasekar , Modrusan Zora
Published: March 2017

Many subtypes of cortical interneurons (CINs) are found in adult mouse cortices, but the mechanism generating their diversity remains elusive. We performed single-cell RNA sequencing on the mouse embryonic medial ganglionic eminence (MGE), the major birthplace for CINs, and on MGE-like cells differentiated from embryonic stem cells. Two distinct cell types were identified as proliferating neural progenitors and immature neurons, both of which comprised sub-populations. Although lineage development of MGE progenitors was reconstructed and immature neurons were characterized as GABAergic, cells that might correspond to precursors of different CINs were not identified. A few non-neuronal cell types were detected, including microglia. In vitro MGE-like cells resembled bona fide MGE cells but expressed lower levels of Foxg1 and Epha4. Together, our data provide detailed understanding of the embryonic MGE developmental program and suggest how CINs are specified.
Discovery of the first dual GSK3β inhibitor/Nrf2 inducer. A new multitarget therapeutic strategy for Alzheimer’s disease
Authors: Gameiro Isabel , Michalska Patrycja , Tenti Giammarco , Cores Ángel , Buendia Izaskun , Rojo Ana I. , Georgakopoulos Nikolaos D. , Hernández-Guijo Jesús M. , Teresa Ramos María , Wells Geoffrey , López Manuela G. , Cuadrado Antonio , Menéndez J. Carlos , León Rafael
Published: March 2017

The formation of neurofibrillary tangles (NFTs), oxidative stress and neuroinflammation have emerged as key targets for the treatment of Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder. These pathological hallmarks are closely related to the over-activity of the enzyme GSK3β and the downregulation of the defense pathway Nrf2-EpRE observed in AD patients. Herein, we report the synthesis and pharmacological evaluation of a new family of multitarget 2,4-dihydropyrano[2,3-c]pyrazoles as dual GSK3β inhibitors and Nrf2 inducers. These compounds are able to inhibit GSK3β and induce the Nrf2 phase II antioxidant and anti-inflammatory pathway at micromolar concentrations, showing interesting structure-activity relationships. The association of both activities has resulted in a remarkable anti-inflammatory ability with an interesting neuroprotective profile on in vitro models of neuronal death induced by oxidative stress and energy depletion and AD. Furthermore, none of the compounds exhibited in vitro neurotoxicity or hepatotoxicity and hence they had improved safety profiles compared to the known electrophilic Nrf2 inducers. In conclusion, the combination of both activities in this family of multitarget compounds confers them a notable interest for the development of lead compounds for the treatment of AD.