julilili42/papers huggingface dataset:
Heterozygote carriers for CNVs inPARK2are at increased risk of Parkinson's disease
2015-07-17

Together with point mutations, homozygous deletions or duplications in PARK2 are responsible for the majority of autosomal recessive juvenile Parkinsonism. It is debated, however, whether heterozygous carriers of these mutations are at increased risk of Parkinson's disease (PD). Our goal was to determine whether heterozygous carriers of copy number variants (CNVs) affecting exons of the PARK2 gene are at risk of PD that is greater than that of non-carriers. We searched for CNVs affecting exons of PARK2 in a sample of 105 749 genotyped Icelanders. In total, 989 carriers, including 24 diagnosed with PD, were identified. The heterozygous carriers were tested for association in a sample of 1415 PD patients and 40 474 controls ≥65 years of age. PD patients were more often heterozygous carriers of PARK2 CNVs than controls [odds ratio (OR) = 1.69, P = 0.03] and compound heterozygous PD patients for a CNV and a missense mutation were not found. Furthermore, we conducted a meta-analysis of studies reporting on case-control samples screened for heterozygous PARK2 CNVs. Ten studies were included in the final analysis, with 4538 cases and 4213 controls. The pooled OR and P-value for the published and Icelandic results showed significant association between PARK2 CNVs and risk of PD (OR = 2.11, P = 2.54 × 10(-6)). Our analysis shows that heterozygous carriers of CNVs affecting exons of PARK2 have greater risk of PD than non-carriers.
Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study: Figure 1.
2015-07-17

Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria.
Retinitis pigmentosa: impact of differentPde6apoint mutations on the disease phenotype
2015-07-17

Mutations in the PDE6A gene can cause rod photoreceptors degeneration and the blinding disease retinitis pigmentosa (RP). While a number of pathogenic PDE6A mutations have been described, little is known about their impact on compound heterozygous situations and potential interactions of different disease-causing alleles. Here, we used a novel mouse model for the Pde6a R562W mutation in combination with an existing line carrying the V685M mutation to generate compound heterozygous Pde6a V685M/R562W animals, exactly homologous to a case of human RP. We compared the progression of photoreceptor degeneration in these compound heterozygous mice with the homozygous V685M and R562W mutants, and additionally with the D670G line that is known for a relatively mild phenotype. We investigated PDE6A expression, cyclic guanosine mono-phosphate accumulation, calpain and caspase activity, in vivo retinal function and morphology, as well as photoreceptor cell death and survival. This analysis confirms the severity of different Pde6a mutations and indicates that compound heterozygous mutants behave like intermediates of the respective homozygous situations. Specifically, the severity of the four different Pde6a situations may be categorized by the pace of photoreceptor degeneration: V685M (fastest) > V685M/R562W > R562W > D670G (slowest). While calpain activity was strongly increased in all four mutants, caspase activity was not. This points to the execution of non-apoptotic cell death and may lead to the identification of new targets for therapeutic interventions. For individual RP patients, our study may help to predict time-courses for Pde6a-related retinal degeneration and thereby facilitate the definition of a window-of-opportunity for clinical interventions.
A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium polonicum AP2T1
2015-07-17

Four quinolinones (1-4; 1 is a new compound) were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium polonicum AP2T1. In addition, five new quinolinone derivatives (5-9) and also 1 were obtained in a trimethylsilyldiazomethane-induced methylation reaction of 4. Their structures were elucidated by spectroscopic analyses. In bioassays, compounds 7 and 5 with lactim structures moderately inhibited the proliferation of human cancer cell line HCT116 (wild-type) with IC<sub>50</sub>-24 h of 8.4 μg/mL and 30.7 μg/mL, respectively; the other compounds displayed weaker inhibition. The p53 gene may play some role in their action as suggested by their much weakened activity towards p53-knockout HCT116 cell line. Besides, 6 and 8 exhibited moderate or weak toxicity to brine shrimp larvae, and 3, 4, 8 and 9 showed weak inhibition against Staphylococcus aureus. It is the first report on elucidation of new compounds with origin of shark-derived fungi.
Chapter 10. Just what is it that makes Pop Art picturebooks so different, so appealing?
2015-07-17

In the 1960s and 1970s the Pop Art movement exerted a great influence on picturebook artists in different European countries (Finland, France, Germany, Poland, Switzerland, and the United Kingdom) and the USA. By referring to various avant-garde movements, such as Dadaism, Expressionism, and Surrealism, and by combining materials chosen from different media (advertisements, comics, film, newspapers, photography, and poster art), the author-illustrators introduced new ideas and concepts into picturebook art, thus crossing the boundaries between popular culture, children’s literature, and modern art. Moreover, Pop Art picturebooks are characterized by an anti-pedagogical approach that encourages the child reader to critically reflect upon moral, political, and pedagogical issues and to revolt against authorities. Extended paratexts explain the artists’ intentions and emphasize the presumption that children usually have more openness to new experiences than adults.
A Complex Signaling Cascade Governs Pristinamycin Biosynthesis in Streptomyces pristinaespiralis
2015-07-18

ABSTRACT Pristinamycin production in Streptomyces pristinaespiralis Pr11 is tightly regulated by an interplay between different repressors and activators. A γ-butyrolactone receptor gene ( spbR ), two TetR repressor genes ( papR3 and papR5 ), three SARP ( S treptomyces a ntibiotic r egulatory p rotein) genes ( papR1 , papR2 , and papR4 ), and a response regulator gene ( papR6 ) are carried on the large 210-kb pristinamycin biosynthetic gene region of Streptomyces pristinaespiralis Pr11. A detailed investigation of all pristinamycin regulators revealed insight into a complex signaling cascade, which is responsible for the fine-tuned regulation of pristinamycin production in S. pristinaespiralis .
Fostering adolescents’ value beliefs for mathematics with a relevance intervention in the classroom.
2015-07-20

Interventions targeting students' perceived relevance of the learning content have been shown to effectively promote student motivation within science classes (e.g., Hulleman & Harackiewicz, 2009). Yet, further research is warranted to understand better how such interventions should be designed in order to be successfully implemented in the classroom setting. A cluster randomized controlled study was conducted to test whether ninth-grade students' value beliefs for mathematics (i.e., intrinsic value, attainment value, utility value, and cost) could be fostered with relevance interventions in the classroom. Eighty-two classrooms were randomly assigned to 1 of 2 experimental conditions or a waiting control condition. Both experimental groups received a 90-min intervention within the classroom on the relevance of mathematics, consisting of a psychoeducational presentation and relevance-inducing tasks (either writing a text or evaluating interview quotations). Intervention effects were evaluated via self-reports of 1,916 participating students 6 weeks and 5 months after the intervention in the classroom. Both intervention conditions fostered more positive value beliefs among students at both time points. Compared with the control condition, classes in the quotations condition reported higher utility value, attainment value, and intrinsic value, and classes in the text condition reported higher utility value. Thus, stronger effects on students' value beliefs were found for the quotations condition than for the text condition. When assessing intervention effects separately for females and males, some evidence for stronger effects for females than for males was found.
The Nature of Culture: an eight-grade model for the evolution and expansion of cultural capacities in hominins and other animals.
2015-07-20

Tracing the evolution of human culture through time is arguably one of the most controversial and complex scholarly endeavors, and a broad evolutionary analysis of how symbolic, linguistic, and cultural capacities emerged and developed in our species is lacking. Here we present a model that, in broad terms, aims to explain the evolution and portray the expansion of human cultural capacities (the EECC model), that can be used as a point of departure for further multidisciplinary discussion and more detailed investigation. The EECC model is designed to be flexible, and can be refined to accommodate future archaeological, paleoanthropological, genetic or evolutionary psychology/behavioral analyses and discoveries. Our proposed concept of cultural behavior differentiates between empirically traceable behavioral performances and behavioral capacities that are theoretical constructs. Based largely on archaeological data (the 'black box' that most directly opens up hominin cultural evolution), and on the extension of observable problem-solution distances, we identify eight grades of cultural capacity. Each of these grades is considered within evolutionary-biological and historical-social trajectories. Importantly, the model does not imply an inevitable progression, but focuses on expansion of cultural capacities based on the integration of earlier achievements. We conclude that there is not a single cultural capacity or a single set of abilities that enabled human culture; rather, several grades of cultural capacity in animals and hominins expanded during our evolution to shape who we are today.
Potential Predictors of Plasma Fibroblast Growth Factor 23 Concentrations: Cross-Sectional Analysis in the EPIC-Germany Study
2015-07-20

In middle-aged men and women traditional and non-traditional CVD risk factors were related to higher FGF23 concentrations. These findings may contribute to the understanding of the potential mechanisms linking increased FGF23 to increased CVD risk.
Leaf traits suggest different ecological strategies for twoQuercusspecies along an altitudinal gradient in the Qinling Mountains
2015-07-20

AbstractLocal-scale study on leaf traits and their relationships in a single species along an environmental gradient is essential for scaling up ecophysiological processes from the leaf to the ecosystem level. Here, we quantified 25 leaf traits of two individual species, Quercus aliena var. acutiserrata (Qa, deciduous) and Quercus spinosa (Qs, evergreen), in the same genus, but with different life-form to investigate the leaf traits and relationship variations within and between species along an altitudinal gradient in the Qinling Mountains. Variations of leaf traits were common along an altitudinal gradient at species level, but with different trends between two species. The relationships between plant functional traits were complex and showed different patterns between two species. Two species show different response patterns and adaptation strategies to environmental gradients. The Qa at high altitude suffers from low temperature stress that breaks its carbon balance and leads to growth restriction, which supports the "source-limitation" hypothesis, while Qs at high altitude possesses an adequate supply of carbon to protect from stress, which supports the "sink- or growth-limitation" hypothesis. The effect of environmental change on leaf traits is greater in leaf form than the genetic relationship.Keywords: Altitudinal gradientLeaf traitsPhenologyQinling MountainsQuercus AcknowledgmentsThis work was supported by S&T Basic Work Program of Ministry of Science and Technology, China (2011FY110300) and Forerunner Projects of the Chinese Academy of Sciences (XDA05050301-4).NotesYongfu Chai and Xiaofei Zhang contributed equally to this work.
Using the Placebo Effect to Isolate Control Mechanisms of Athletic Performance: A Research Protocol
2015-07-20

Placebo effects are common in all areas of medicine and beyond and thus, are also present when ergogenic aids are used to enhance performance in athletes. While they usually are regarded as secondary and a nuisance in relation to performance-improving nutritional supplements, we here propose to utilize them to investigate central control mechanisms of athletic performance. Following a brief review of the current literature on placebo effects in sports, we outline a research protocol designed to understand the neurobiological basis of endurance performance, limiting factors and the integration of central and peripheral fatigue mechanisms. A placebo response to ergogenic aids will be elicited to isolate and study both central and peripheral components of performance regulation. This protocol employs endurance performance measurements, electroencephalography, functional near-infrared spectroscopy and ratings of perceived exertion in order to quantify the performance altering placebo response elicited by a nutritional ergogenic aid. A model is proposed integrating the placebo response with current theories of performance determining and limiting factors such as the central governor model and the central fatigue hypothesis. The first experiment is concerned with the influence of the mode of administration of an ergogenic aid on endurance performance. In the second experiment, the cortical processes underlying increased motor performance will be investigated using electroencephalography. The third experiment will employ functional near-infrared spectroscopy to look at the integration of cortico-muscular feed forward and feedback signaling pathways mediating fatigue. This protocol provides an integrative approach for neuroscience and sports science research, investigating cortical processes involved in the placebo induced exploitation of residual central and peripheral resources causing better athletic performance. It also will affect prevention and treatment of diseases which may be caused by a lack of physical activity or which may cause a decrease in the ability to be physically active.
Contests vs. Piece Rates in Product Market Competition
2015-07-20

We study product market competition between firm owners (principals) where workers (agents) decide on their efforts and, hence, on output levels. Two worker compensation schemes are compared: a piece rate compensation as a benchmark when workers’ output performance is verifiable, and a contest-based compensation scheme with variable, revenue-based prizes when it is only verifiable who the best performing worker is, i.e., only ’contest performance’ is verifiable.Without rivalry between firms, the two compensation schemes lead to the same results. In case of product market competition, however, contest-based compensation schemes lead to more employment, more production, and lower firm profits. The reduction in profits represents the cost of being only able to verify workers’ contest performance instead of output performance.
Solutions for Low and High Accuracy Mass Spectrometric Data Matching: A Data-Driven Annotation Strategy in Nontargeted Metabolomics
2015-07-21

Ultra high pressure liquid chromatography coupled to mass spectrometry (UHPLC-MS) has become a widespread analytical technique in metabolomics investigations, however the benefit of high-performance chromatographic separation is often blunted due to insufficient mass spectrometric accuracy. A strategy that allows for the matching of UHPLC-MS data to highly accurate direct infusion electrospray ionization (DI-ESI) Fourier transform ion cyclotron resonance/mass spectrometry (FTICR/MS) data is developed in this manuscript. Mass difference network (MDiN) based annotation of FTICR/MS data and matching to unique UHPLC-MS peaks enables the consecutive annotation of the chromatographic data set. A direct comparison of experimental m/z values provided no basis for the matching of both platforms. The matching of annotation-based exact neutral masses finally enabled the integration of platform specific multivariate statistical evaluations, minimizing the danger to compare artifacts generated on either platform. The approach was developed on a non-alcoholic fatty liver disease (NAFLD) data set.
About the Order of Cart and Horse, Among Others – Estoppel in the Jurisprudence of International Investment Arbitration Tribunals
2015-07-21

A quantitative and qualitative study of international investment arbitration case law employing the concept of estoppel reveals investment tribunals’ inconsistency with regard to its requirements. This contribution discusses possible reasons why tribunals often deviate from what appears to be the established view in the jurisprudence of the International Court of Justice (‘ICJ’) and in international law scholarship and why they do not explain their preference for the one or the other view. In fact, the often striking lack of reasoning in this regard begs the question as to the order of approach chosen and outcome produced. In the interest of doctrinal and jurisprudential consistency, arbitrators should be more transparent as to their choice of view and as to the reasons for choosing it over another one. This will sharpen the concept of estoppel both in international investment law in particular and in public international law in general.
Evidence‐based (S3) Guideline on (anogenital) Lichen sclerosus
2015-07-22

Abstract Lichen sclerosus (LS) is an inflammatory skin disease that usually involves the anogenital area. All patients with symptoms or signs suspicious of lichen sclerosus should be seen at least once initially by a physician with a special interest in the disease in order to avoid delay in diagnosis, as early treatment may cure the disease in some and reduce or prevent scarring. The diagnosis is made clinically in most cases. Biopsies should only be performed under certain circumstances. The gold standard for treatment remains potent to very potent topical steroids; however, mild and moderate disease in boys and men may be cured by circumcision. Certain triggers should be avoided. http://www.euroderm.org/images/stories/guidelines/2014/S3-Guideline-on-Lichen-sclerosus.pdf http://www.awmf.org/fachgesellschaften/mitgliedsgesellschaften/visitenkarte/fg/deutsche-gesellschaft-fuer-gynaekologie-und-geburtshilfe-dggg.html .
STAT3 regulated ARF expression suppresses prostate cancer metastasis
2015-07-22

Abstract Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten -deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19 ARF as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF–Mdm2–p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14 ARF expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.
Asteroid flux towards circumprimary habitable zones in binary star systems
2015-07-22

So far, multiple stellar systems harbor more than 130 extra solar planets. Dynamical simulations show that the outcome of planetary formation process can lead to various planetary architecture (i.e. location, size, mass and water content) when the star system is single or double. In the late phase of planetary formation, when embryo-sized objects dominate the inner region of the system, asteroids are also present and can provide additional material for objects inside the habitable zone (hereafter HZ). In this study, we make a comparison of several binary star systems and their efficiency to move icy asteroids from beyond the snow-line into orbits crossing the HZ. We modeled a belt of 10000 asteroids (remnants from the late phase of planetary formation process) beyond the snow-line. The planetesimals are placed randomly around the primary star and move under the gravitational influence of the two stars and a gas giant. As the planetesimals do not interact with each other, we divided the belt into 100 subrings which were separately integrated. In this statistical study, several double star configurations with a G-type star as primary are investigated. Our results show that small bodies also participate in bearing a non-negligible amount of water to the HZ. The proximity of a companion moving on an eccentric orbit increases the flux of asteroids to the HZ, which could result into a more efficient water transport on a short timescale, causing a heavy bombardment. In contrast to asteroids moving under the gravitational perturbations of one G-type star and a gas giant, we show that the presence of a companion star can not only favor a faster depletion of our disk of planetesimals but can also bring 4 -- 5 times more water into the whole HZ.
Entorrhizomycota: A New Fungal Phylum Reveals New Perspectives on the Evolution of Fungi
2015-07-22

Entorrhiza is a small fungal genus comprising 14 species that all cause galls on roots of Cyperaceae and Juncaceae. Although this genus was established 130 years ago, crucial questions on the phylogenetic relationships and biology of this enigmatic taxon are still unanswered. In order to infer a robust hypothesis about the phylogenetic position of Entorrhiza and to evaluate evolutionary trends, multiple gene sequences and morphological characteristics of Entorrhiza were analyzed and compared with respective findings in Fungi. In our comprehensive five-gene analyses Entorrhiza appeared as a highly supported monophyletic lineage representing the sister group to the rest of the Dikarya, a phylogenetic placement that received but moderate maximum likelihood and maximum parsimony bootstrap support. An alternative maximum likelihood tree with the constraint that Entorrhiza forms a monophyletic group with Basidiomycota could not be rejected. According to the first phylogenetic hypothesis, the teliospore tetrads of Entorrhiza represent the prototype of the dikaryan meiosporangium. The alternative hypothesis is supported by similarities in septal pore structure, cell wall and spindle pole bodies. Based on the isolated phylogenetic position of Entorrhiza and its peculiar combination of features related to ultrastructure and reproduction mode, we propose a new phylum Entorrhizomycota, for the genus Entorrhiza, which represents an apparently widespread group of inconspicuous fungi.