Genotype and antibiotic resistance analyses of Campylobacter isolates from ceca and carcasses of slaughtered broiler flocks

To obtain genetic information about Campylobacter jejuni and Campylobacter coli from broilers and carcasses at slaughterhouses, we analyzed and compared 340 isolates that were collected in 2008 from the cecum right after slaughter or from the neck skin after processing. We performed rpoB sequence-based identification, multilocus sequence typing (MLST), and flaB sequence-based typing; we additionally analyzed mutations within the 23S rRNA and gyrA genes that confer resistance to macrolide and quinolone antibiotics, respectively. The rpoB-based identification resulted in a distribution of 72.0% C. jejuni and 28.0% C. coli. The MLST analysis revealed that there were 59 known sequence types (STs) and 6 newly defined STs. Most of the STs were grouped into 4 clonal complexes (CC) that are typical for poultry (CC21, CC45, CC257, and CC828), and these represented 61.8% of all of the investigated isolates. The analysis of 95 isolates from the cecum and from the corresponding carcass neck skin covered 44 different STs, and 54.7% of the pairs had matching genotypes. The data indicate that cross-contamination from various sources during slaughter may occur, although the majority of Campylobacter contamination on carcasses appeared to originate from the slaughtered flock itself. Mutations in the 23S rRNA gene were found in 3.1% of C. coli isolates, although no mutations were found in C. jejuni isolates. Mutations in the gyrA gene were observed in 18.9% of C. jejuni and 26.8% of C. coli isolates, which included two C. coli strains that carried mutations conferring resistance to both classes of antibiotics. A relationship between specific genotypes and antibiotic resistance/susceptibility was observed.

Uncovering the dynamics of cardiac systems using stochastic pacing and frequency domain analyses

Alternans of cardiac action potential duration (APD) is a well-known arrhythmogenic mechanism which results from dynamical instabilities. The propensity to alternans is classically investigated by examining APD restitution and by deriving APD restitution slopes as predictive markers. However, experiments have shown that such markers are not always accurate for the prediction of alternans. Using a mathematical ventricular cell model known to exhibit unstable dynamics of both membrane potential and Ca2+ cycling, we demonstrate that an accurate marker can be obtained by pacing at cycle lengths (CLs) varying randomly around a basic CL (BCL) and by evaluating the transfer function between the time series of CLs and APDs using an autoregressive-moving-average (ARMA) model. The first pole of this transfer function corresponds to the eigenvalue (λalt) of the dominant eigenmode of the cardiac system, which predicts that alternans occurs when λalt≤−1. For different BCLs, control values of λalt were obtained using eigenmode analysis and compared to the first pole of the transfer function estimated using ARMA model fitting in simulations of random pacing protocols. In all versions of the cell model, this pole provided an accurate estimation of λalt. Furthermore, during slow ramp decreases of BCL or simulated drug application, this approach predicted the onset of alternans by extrapolating the time course of the estimated λalt. In conclusion, stochastic pacing and ARMA model identification represents a novel approach to predict alternans without making any assumptions about its ionic mechanisms. It should therefore be applicable experimentally for any type of myocardial cell.

Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders

Very recently, heterozygous mutations in the genes encoding transforming growth factor beta receptors I (TGFBR1) and II (TGFBR2) have been reported in Loeys-Dietz aortic aneurysm syndrome (LDS). In addition, dominant TGFBR2 mutations have been identified in Marfan syndrome type 2 (MFS2) and familial thoracic aortic aneurysms and dissections (TAAD). In the past, mutations of these genes were associated with atherosclerosis and several human cancers. Here, we report a total of nine novel and one known heterozygous sequence variants in the TGFBR1 and TGFBR2 genes in nine of 70 unrelated individuals with MFS-like phenotypes who previously tested negative for mutations in the gene encoding the extracellular matrix protein fibrillin-1 (FBN1). To assess the pathogenic impact of these sequence variants, in silico analyses were performed by the PolyPhen, SIFT, and Fold-X algorithms and by means of a 3D homology model of the TGFBR2 kinase domain. Our results showed that in all but one of the patients the pathogenic effect of at least one sequence variant is highly probable (c.722C > T, c.799A > C, and c.1460G > A in TGFBR1 and c.773T > G, c.1106G > T, c.1159G > A, c.1181G > A, and c.1561T > C in TGFBR2). These deleterious alleles occurred de novo or segregated with the disease in the families, indicating a causative association between the sequence variants and clinical phenotypes. Since TGFBR2 mutations found in patients with MFS-related disorders cannot be distinguished from heterozygous TGFBR2 mutations reported in tumor samples, we emphasize the importance of segregation analysis in affected families. In order to be able to find the mutation that is indeed responsible for a MFS-related phenotype, we also propose that genetic testing for sequence alterations in TGFBR1 and TGFBR2 should be complemented by mutation screening of the FBN1 gene.

Plant ion channels: gene families, physiology, and functional genomics analyses

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland

Switzerland has a complex human immunodeficiency virus (HIV) epidemic involving several populations. We examined transmission of HIV type 1 (HIV-1) in a national cohort study. Latent class analysis was used to identify socioeconomic and behavioral groups among 6,027 patients enrolled in the Swiss HIV Cohort Study between 2000 and 2011. Phylogenetic analysis of sequence data, available for 4,013 patients, was used to identify transmission clusters. Concordance between sociobehavioral groups and transmission clusters was assessed in correlation and multiple correspondence analyses. A total of 2,696 patients were infected with subtype B, 203 with subtype C, 196 with subtype A, and 733 with recombinant subtypes (mainly CRF02_AG and CRF01_AE). Latent class analysis identified 8 patient groups. Most transmission clusters of subtype B were shared between groups of gay men (groups 1-3) or between the heterosexual groups "heterosexual people of lower socioeconomic position" (group 4) and "injection drug users" (group 8). Clusters linking homosexual and heterosexual groups were associated with "older heterosexual and gay people on welfare" (group 5). "Migrant women in heterosexual partnerships" (group 6) and "heterosexual migrants on welfare" (group 7) shared non-B clusters with groups 4 and 5. Combining approaches from social and molecular epidemiology can provide insights into HIV-1 transmission and inform the design of prevention strategies.

The palaeolimnology of Soppensee (Central Switzerlabnd), as evidenced by diatom, pollen, and fossil-pigment analyses

The development of Soppensee (Central Switzerland, 596 m a.s.l.) has been reconstructed using algal remains such as diatoms, chlorophytes and fossil pigments, as well as the pollen and spores of macrophytes. Sediment accumulation in Soppensee began at the end of the last glacial period, approximately 15,000 yrs ago. During the Oldest Dryas biozone (> 12,700 radiocarbon yrs B.P.) the lake had low primary productivity. After reforestation with birch and later pine, around 12,700 B.P., phases of summer anoxia occurred in the lake. These anoxic conditions were most probably caused by additional carbon input from the catchment, as well as longer phases of stratification due to reduced wind exposure caused by the sheltering effect of increased tree cover. From the Younger Dryas biozone (10,800 to 10,000 radiocarbon yrs B.P.) onwards, Soppensee became meromictic for several millennia.

Late-glacial and Holocene vegetation history and dynamics as shown by pollen and plant macrofossil analyses in annually laminated sediments from Soppensee, central Switzerland

The palynostratigraphy of two sediment cores from Soppensee, Central Switzerland (596 m asl) was correlated with nine regional pollen assemblage zones defined for the Swiss Plateau. This biostratigraphy shows that the sedimentary record of Soppensee includes the last 15 000 years, i.e. the entire Late-glacial and Holocene environmental history. The vegetation history of the Soppensee catchment was inferred by pollen and plant-macrofossil analyses on three different cores taken in the deepest part of the lake basin (27 m). On the basis of a high-resolution varve and calibrated radiocarbonchronology it was possible to estimate pollen accumulation rates, which together with the pollen percentage data, formed the basis for the interpretation of the past vegetation dynamics. The basal sediment dates back to the last glacial. After reforestation with juniper and birch at ca. 12 700 B.P., the vegetation changed at around 12 000 B.P. to a pine-birch woodland and at the onset of the Holocene to a mixed deciduous forest. At ca. 7000 B.P., fir expanded and dominated the vegetation with beech becoming predominant at ca. 50014C-years later until sometime during the Iron Age. Large-scale deforestation, especially during the Middle Ages, altered the vegetation cover drastically. During the Late-glacial period two distinct regressive phases in vegetation development are demonstrated, namely, the Aegelsee oscillation (equivalent to the Older Dryas biozone) and the Younger Dryas biozone. No unambiguous evidence for Holocene climatic change was detected at Soppensee. Human presence is indicated by early cereal pollen and distinct pulses of forest clearance as a result of human activity can be observed from the Neolithic period onwards.

Twist and shout: one decade of meta-analyses of erythropoiesis-stimulating agents in cancer patients

Anemia associated with cancer and cancer therapy is a common and important issue in the treatment of patients with malignant disease. Conventionally, blood transfusions are used to treat severe cancer-related anemia. Short- and long-acting preparations of recombinant human erythropoiesis-stimulating agents (ESAs) offer an alternative treatment option. Multiple studies and subsequent meta-analyses have demonstrated that ESA treatment increases hemoglobin levels and reduces the likelihood of transfusion for a proportion of treated patients. However, studies that attempted to evaluate whether ESAs improve tumor response and survival have generated conflicting evidence. Results of smaller trials reporting improved survival outcomes were contradicted by large randomized controlled trials that reported more deaths in patients receiving ESAs. In addition, there is strong evidence that cancer patients receiving ESAs have an increased risk of thromboembolic and cardiovascular events. We herein review the main meta-analyses published in the field, their strengths and weaknesses, their contribution to patient management and future perspectives for systematic reviews.

Evaluation and quantification of spectral information in tissue by confocal microscopy

A confocal imaging and image processing scheme is introduced to visualize and evaluate the spatial distribution of spectral information in tissue. The image data are recorded using a confocal laser-scanning microscope equipped with a detection unit that provides high spectral resolution. The processing scheme is based on spectral data, is less error-prone than intensity-based visualization and evaluation methods, and provides quantitative information on the composition of the sample. The method is tested and validated in the context of the development of dermal drug delivery systems, introducing a quantitative uptake indicator to compare the performances of different delivery systems is introduced. A drug penetration study was performed in vitro. The results show that the method is able to detect, visualize and measure spectral information in tissue. In the penetration study, uptake efficiencies of different experiment setups could be discriminated and quantitatively described. The developed uptake indicator is a step towards a quantitative assessment and, in a more general view apart from pharmaceutical research, provides valuable information on tissue composition. It can potentially be used for clinical in vitro and in vivo applications.

Building a soil spectral library for Tajikistan comparing local and global modeling approaches

Over the last ~20 years, soil spectral libraries storing near-infrared reflectance (NIR) spectra from diverse soil samples have been built for many places, since almost 10 years also for Tajikistan. Many calibration approaches have been reported and used for prediction from large and heterogeneous libraries, but most are hampered by the high diversity of the soils, where the mineral background is heavily influencing spectral features. In such cases, local learning strategies have the advantage of building locally adapted calibrations, which can deal better with nonlinearities. Therefore, it was our major aim to identify the most efficient approach to develop an accurate and stable locally weigthed calibration model using a spectral library compiled over the past years. Keywords: Tajikistan, Near-Infrared spectroscopy (NIRS), soil organic carbon, locally weighted regression, regional and local spectral library.

Geomorphology and spectrophotometry of Philae's landing site on comet 67P/Churyumov-Gerasimenko

Context. On 12 November 2014 the European mission Rosetta succeeded in delivering a lander, named Philae, on the surface of one of the smallest, low-gravity and most primitive bodies of the solar system, the comet 67P/Churyumov-Gerasimenko (67P). Aims. The aim of this paper is to provide a comprehensive geomorphological and spectrophotometric analysis of Philae's landing site (Agilkia) to give an essential framework for the interpretation of its in situ measurements. Methods. OSIRIS images, coupled with gravitational slopes derived from the 3D shape model based on stereo-photogrammetry were used to interpret the geomorphology of the site. We adopted the Hapke model, using previously derived parameters, to photometrically correct the images in orange filter (649.2 nm). The best approximation to the Hapke model, given by the Akimov parameter-less function, was used to correct the reflectance for the effects of viewing and illumination conditions in the other filters. Spectral analyses on coregistered color cubes were used to retrieve spectrophotometric properties. Results. The landing site shows an average normal albedo of 6.7% in the orange filter with variations of similar to 15% and a global featureless spectrum with an average red spectral slope of 15.2%/100 nm between 480.7 nm (blue filter) and 882.1 nm (near-IR filter). The spatial analysis shows a well-established correlation between the geomorphological units and the photometric characteristics of the surface. In particular, smooth deposits have the highest reflectance a bluer spectrum than the outcropping material across the area. Conclusions. The featureless spectrum and the redness of the material are compatible with the results by other instruments that have suggested an organic composition. The observed small spectral variegation could be due to grain size effects. However, the combination of photometric and spectral variegation suggests that a compositional differentiation is more likely. This might be tentatively interpreted as the effect of the efficient dust-transport processes acting on 67P. High-activity regions might be the original sources for smooth fine-grained materials that then covered Agilkia as a consequence of airfall of residual material. More observations performed by OSIRIS as the comet approaches the Sun would help interpreting the processes that work at shaping the landing site and the overall nucleus.