The Zagier polynomials. Part II: Arithmetic properties of coefficients

The modified Bernoulli numbers \begin{equation*} B_{n}^{*} = \sum_{r=0}^{n} \binom{n+r}{2r} \frac{B_{r}}{n+r}, \quad n > 0 \end{equation*} introduced by D. Zagier in 1998 were recently extended to the polynomial case by replacing $B_{r}$ by the Bernoulli polynomials $B_{r}(x)$. Arithmetic properties of the coefficients of these polynomials are established. In particular, the 2-adic valuation of the modified Bernoulli numbers is determined. A variety of analytic, umbral, and asymptotic methods is used to analyze these polynomials

A P2X receptor from the tardigrade species Hypsibius dujardini with fast kinetics and sensitivity to zinc and copper

<p>Abstract</p> <p>Background</p> <p>Orthologs of the vertebrate ATP gated P2X channels have been identified in <it>Dictyostelium </it>and green algae, demonstrating that the emergence of ionotropic purinergic signalling was an early event in eukaryotic evolution. However, the genomes of a number of animals including <it>Drosophila melanogaster </it>and <it>Caenorhabditis elegans</it>, both members of the Ecdysozoa superphylum, lack P2X-like proteins, whilst other species such as the flatworm <it>Schistosoma mansoni </it>have P2X proteins making it unclear as to what stages in evolution P2X receptors were lost. Here we describe the functional characterisation of a P2X receptor (<it>Hd</it>P2X) from the tardigrade <it>Hypsibius dujardini </it>demonstrating that purinergic signalling is preserved in some ecdysozoa.</p> <p>Results</p> <p>ATP (EC₅₀~44.5 μM) evoked transient inward currents in <it>Hd</it>P2X with millisecond rates of activation and desensitisation. <it>Hd</it>P2X is antagonised by pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid (IC₅₀15.0 μM) and suramin (IC₅₀22.6 μM) and zinc and copper inhibit ATP-evoked currents with IC₅₀values of 62.8 μM and 19.9 μM respectively. Site-directed mutagenesis showed that unlike vertebrate P2X receptors, extracellular histidines do not play a major role in coordinating metal binding in <it>Hd</it>P2X. However, H306 was identified as playing a minor role in the actions of copper but not zinc. Ivermectin potentiated responses to ATP with no effect on the rates of current activation or decay.</p> <p>Conclusion</p> <p>The presence of a P2X receptor in a tardigrade species suggests that both nematodes and arthropods lost their P2X genes independently, as both traditional and molecular phylogenies place the divergence between Nematoda and Arthropoda before their divergence from Tardigrada. The phylogenetic analysis performed in our study also clearly demonstrates that the emergence of the family of seven P2X channels in human and other mammalian species was a relatively recent evolutionary event that occurred subsequent to the split between vertebrates and invertebrates. Furthermore, several characteristics of <it>Hd</it>P2X including fast kinetics with low ATP sensitivity, potentiation by ivermectin in a channel with fast kinetics and distinct copper and zinc binding sites not dependent on histidines make <it>Hd</it>P2X a useful model for comparative structure-function studies allowing a better understanding of P2X receptors in higher organisms.</p

Do pesticide and pathogen interactions drive wild bee declines?

There is clear evidence for wild insect declines globally. Habitat loss, climate change, pests, pathogens and environmental pollution have all been shown to cause detrimental effects on insects. However, interactive effects between these stressors may be the key to understanding reported declines. Here, we review the literature on pesticide and pathogen interactions for wild bees, identify knowledge gaps, and suggest avenues for future research fostering mitigation of the observed declines. The limited studies available suggest that effects of pesticides most likely override effects of pathogens. Bees feeding on flowers and building sheltered nests, are likely less adapted to toxins compared to other insects, which potential susceptibility is enhanced by the reduced number of genes encoding detoxifying enzymes compared with other insect species. However, to date all 10 studies using a fully-crossed design have been conducted in the laboratory on social bees using Crithidia spp. or Nosema spp., identifying an urgent need to test solitary bees and other pathogens. Similarly, since laboratory studies do not necessarily reflect field conditions, semi-field and field studies are essential if we are to understand these interactions and their potential effects in the real-world. In conclusion, there is a clear need for empirical (semi-)field studies on a range of pesticides, pathogens, and insect species to better understand the pathways and mechanisms underlying their potential interactions, in particular their relevance for insect fitness and population dynamics. Such data are indispensable to drive forward robust modelling of interactive effects in different environmental settings and foster predictive science. This will enable pesticide and pathogen interactions to be put into the context of other stressors more broadly, evaluating their relative importance in driving the observed declines of wild bees and other insects. Ultimately, this will enable the development of more effective mitigation measures to protect bees and the ecosystem services they supply

Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort.

HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival. Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC) and the concordance-index (c-index): BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4%) was the leading etiological factor followed by viral hepatitis C (18.8%). Median survival was 18.1 months (95%-CI: 15.2-22.2). Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS) was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71), surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66). The unidimensional scores TNM (AIC 2342, c-index 0.64) and Child-Pugh (AIC 2369, c-index 0.63) performed in an inferior fashion. Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients

The UK myotonic dystrophy patient registry: facilitating and accelerating clinical research

Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy worldwide with complex, multi-systemic, and progressively worsening symptoms. There is currently no treatment for this inherited disorder and research can be challenging due to the rarity and variability of the disease. The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information. For this cross-sectional “snapshot” analysis, 556 patients with a confirmed diagnosis of DM1 registered between May 2012 and July 2016 were included. An almost even distribution was seen between genders and a broad range of ages was present from 8 months to 78 years, with the largest proportion between 30 and 59 years. The two most frequent symptoms were fatigue and myotonia, reported by 79 and 78% of patients, respectively. The severity of myotonia correlated with the severity of fatigue as well as mobility impairment, and dysphagia occurred mostly in patients also reporting myotonia. Men reported significantly more frequent severe myotonia, whereas severe fatigue was more frequently reported by women. Cardiac abnormalities were diagnosed in 48% of patients and more than one-third of them needed a cardiac implant. Fifteen percent of patients used a non-invasive ventilation and cataracts were removed in 26% of patients, 65% of which before the age of 50 years. The registry’s primary aim was to facilitate and accelerate clinical research. However, these data also allow us to formulate questions for hypothesis-driven research that may lead to improvements in care and treatment

Meta-analysis of Arabidopsis KANADI1 direct target genes identifies basic growth-promoting module acting upstream of hormonal signaling pathways

An intricate network of antagonistically acting transcription factors mediates the formation of a flat leaf lamina of Arabidopsis (Arabidopsis thaliana) plants. In this context, members of the class III homeodomain leucine zipper (HD-ZIPIII) transcription factor family specify the adaxial domain (future upper side) of the leaf, while antagonistically acting KANADI transcription factors determine the abaxial domain (future lower side). Here, we used a messenger RNA sequencing approach to identify genes regulated by KANADI1 (KAN1) and subsequently performed a meta-analysis combining our data sets with published genome-wide data sets. Our analysis revealed that KAN1 acts upstream of several genes encoding auxin biosynthetic enzymes. When exposed to shade, we found three YUCCA genes, YUC2, YUC5, and YUC8, to be transcriptionally up-regulated, which correlates with an increase in the levels of free auxin. When ectopically expressed, KAN1 is able to transcriptionally repress these three YUC genes and thereby block shade-induced auxin biosynthesis. Consequently, KAN1 is able to strongly suppress shade-avoidance responses. Taken together, we hypothesize that HD-ZIPIII/KAN form the basis of a basic growth-promoting module. Hypocotyl extension in the shade and outgrowth of new leaves both involve auxin synthesis and signaling, which are under the direct control of HD-ZIPIII/KAN.This work was supported by the European Union (Marie-Curie International Reintegration grant no. 256502 to S.W.), the Deutsche Forschungsgemeinschaft Collaborative Research Centre (grant no. SFB1101 to S.W.), the European Research Council (grant no. 336295 to S.W.), and the Spanish MINECO (grant no. BIO2011–23489 to J.F.M.-G.).Peer reviewe

Cloud native robotic applications with GPU sharing on Kubernetes

Accepted submission at the Workshop "Cloud and Fog Robotics In The Age of Deep Learning".In this paper we discuss our experience in teaching the Robotic Applications Programming course at ZHAW combining the use of a Kubernetes (k8s) cluster and real, heterogeneous, robotic hardware. We discuss the main advantages of our solutions in terms of seamless "simulation to real'' experience for students and the main shortcomings we encountered with networking and sharing GPUs to support deep learning workloads. We describe the current and foreseen alternatives to avoid these drawbacks in future course editions and propose a more cloud-native approach to deploying multiple robotics applications on a k8s cluster

Take Part Prototype: Creating New Ways of Participation Through Augmented and Virtual Reality [in press]

Famous examples like the Amazon headquarter in New York City or the Stuttgart 21 train station demonstrate that construction projects are often subjects of common interest and can therefore produce protests if citizens feel unheard in urban planning. In this manuscript, we would therefore like to investigate whether e-participation can be used as a tool to foster citizen involvement in construction projects that are of public interest. To this end, we present a prototype that combines participation with augmented and virtual reality. While offering a source for a better understanding of construction processes, our prototype allows users to bring in their own design suggestions and discuss these with others. With this prototype paper, we thus want to demonstrate how augmented and virtual reality can lay the ground for innovative ways of political participation that would offer great potential for project initiators and citizens

Horizontal Gene Acquisitions, Mobile Element Proliferation, and Genome Decay in the Host-Restricted Plant Pathogen \u3ci\u3eErwinia Tracheiphila\u3c/i\u3e

Modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains of the cucurbit bacterial wilt pathogen Erwinia tracheiphila (Enterobacteriaceae) isolated from infected squash plants in New York, Pennsylvania, Kentucky, and Michigan. These genomes exhibit a high proportion of recent horizontal gene acquisitions, invasion and remarkable amplification of mobile genetic elements, and pseudogenization of approximately 20% of the coding sequences. These genome attributes indicate that E. tracheiphila recently emerged as a host-restricted pathogen. Furthermore, chromosomal rearrangements associated with phage and transposable element proliferation contribute to substantial differences in gene content and genetic architecture between the six E. tracheiphila strains and other Erwinia species. Together, these data lead us to hypothesize that E. tracheiphila has undergone recent evolution through both genome decay (pseudogenization) and genome expansion (horizontal gene transfer and mobile element amplification). Despite evidence of dramatic genomic changes, the six strains are genetically monomorphic, suggesting a recent population bottleneck and emergence into E. tracheiphila’s current ecological niche

Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae)

Despite knowledge that concerted evolution of high-copy loci is often imperfect, studies that investigate the extent of intragenomic polymorphisms and comparisons across a large number of species are rarely made. We present a bioinformatic pipeline for characterizing polymorphisms within an individual among copies of a high-copy locus. Results are presented for nuclear ribosomal DNA (nrDNA) across the milkweed genus, Asclepias. The 18S-26S portion of the nrDNA cistron of Asclepias syriaca served as a reference for assembly of the region from 124 samples representing 90 species of Asclepias. Reads were mapped back to each individual’s consensus and at each position reads differing from the consensus were tallied using a custom perl script. Low frequency polymorphisms existed in all individuals (mean = 5.8%). Most nrDNA positions (91%) were polymorphic in at least one individual, with polymorphic sites being less frequent in subunit regions and loops. Highly polymorphic sites existed in each individual, with highest abundance in the “noncoding” ITS regions. Phylogenetic signal was present in the distribution of intragenomic polymorphisms across the genus. Intragenomic polymorphisms in nrDNA are common in Asclepias, being found at higher frequency than any other study to date. The high and variable frequency of polymorphisms across species highlights concerns that phylogenetic applications of nrDNA may be error-prone. The new analytical approach provided here is applicable to other taxa and other high-copy regions characterized by low coverage genome sequencing (genome skimming).This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by PeerJ. The published article can be found at: https://peerj.com/.Keywords: Evolutionary studies, Bioinformatics, Intragenomic polymorphism, Plant science, Asclepias, Genomics, High-copy, Partial SNP (pSNP), ITS, Genetics, Concerted evolution, Nuclear ribosomal DNA (nrDNA), Intra-individual site polymorphism, Genome skimming, 2IS