A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m−2 plus doxorubicin 60 mg m−2 (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m−2 plus cisplatin 70 mg m−2 (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with ⩾73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy

Preferential Occupancy of R2 Retroelements on the B Chromosomes of the Grasshopper Eyprepocnemis plorans

R2 non-LTR retrotransposons exclusively insert into the 28S rRNA genes of their host, and are expressed by co-transcription with the rDNA unit. The grasshopper Eyprepocnemis plorans contains transcribed rDNA clusters on most of its A chromosomes, as well as non-transcribed rDNA clusters on the parasitic B chromosomes found in many populations. Here the structure of the E. plorans R2 element, its abundance relative to the number of rDNA units and its retrotransposition activity were determined. Animals screened from five populations contained on average over 12,000 rDNA units on their A chromosomes, but surprisingly only about 100 R2 elements. Monitoring the patterns of R2 insertions in individuals from these populations revealed only low levels of retrotransposition. The low rates of R2 insertion observed in E. plorans differ from the high levels of R2 insertion previously observed in insect species that have many fewer rDNA units. It is proposed that high levels of R2 are strongly selected against in E. plorans, because the rDNA transcription machinery in this species is unable to differentiate between R2-inserted and uninserted units. The B chromosomes of E. plorans contain an additional 7,000 to 15,000 rDNA units, but in contrast to the A chromosomes, from 150 to over 1,500 R2 elements. The higher concentration of R2 in the inactive B chromosomes rDNA clusters suggests these chromosomes can act as a sink for R2 insertions thus further reducing the level of insertions on the A chromosomes. These studies suggest an interesting evolutionary relationship between the parasitic B chromosomes and R2 elements.This study was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (CGL2009-11917) and Plan Andaluz de Investigacion (CVI-6649), and was partially performed by FEDER funds and a grant from the National Institutes of Health (GM42790)

Time-resolved imaging of magnetic vortex dynamics using holography with extended reference autocorrelation by linear differential operator

The magnetisation dynamics of the vortex core and Landau pattern of magnetic thin-film elements has been studied using holography with extended reference autocorrelation by linear differential operator (HERALDO). Here we present the first time-resolved x-ray measurements using this technique and investigate the structure and dynamics of the domain walls after excitation with nanosecond pulsed magnetic fields. It is shown that the average magnetisation of the domain walls has a perpendicular component that can change dynamically depending on the parameters of the pulsed excitation. In particular, we demonstrate the formation of wave bullet-like excitations, which are generated in the domain walls and can propagate inside them during the cyclic motion of the vortex core. Based on numerical simulations we also show that, besides the core, there are four singularities formed at the corners of the pattern. The polarisation of these singularities has a direct relation to the vortex core, and can be switched dynamically by the wave bullets excited with a magnetic pulse of specific parameters. The subsequent dynamics of the Landau pattern is dependent on the particular configuration of the polarisations of the core and the singularities

Effect of Biocontrol Agent Pseudomonas fluorescens 2P24 on Soil Fungal Community in Cucumber Rhizosphere Using T-RFLP and DGGE

Fungi and fungal community play important roles in the soil ecosystem, and the diversity of fungal community could act as natural antagonists of various plant pathogens. Biological control is a promising method to protect plants as chemical pesticides may cause environment pollution. Pseudomonas fluorescens 2P24 had strong inhibitory on Rastonia solanacearum, Fusarium oxysporum and Rhizoctonia solani, etc., and was isolated from the wheat rhizosphere take-all decline soils in Shandong province, China. However, its potential effect on soil fungal community was still unknown. In this study, the gfp-labeled P. fluorescens 2P24 was inoculated into cucumber rhizosphere, and the survival of 2P24 was monitored weekly. The amount decreased from 108 to 105 CFU/g dry soils. The effect of 2P24 on soil fungal community in cucumber rhizosphere was investigated using T-RFLP and DGGE. In T-RFLP analysis, principle component analysis showed that the soil fungal community was greatly influenced at first, digested with restriction enzyme Hinf I and Taq I. However, there was little difference as digested by different enzymes. DGGE results demonstrated that the soil fungal community was greatly shocked at the beginning, but it recovered slowly with the decline of P. fluorescens 2P24. Four weeks later, there was little difference between the treatment and control. Generally speaking, the effect of P. fluorescens 2P24 on soil fungal community in cucumber rhizosphere was just transient

Does public awareness increase support for invasive species management?:Promising evidence across taxa and landscape types

Management of invasive species often raises substantial conflicts of interest. Since such conflicts can hamper proposed management actions, managers, decision makers and researchers increasingly recognize the need to consider the social dimensions of invasive species management. In this exploratory study, we aimed (1) to explore whether species’ taxonomic position (i.e. animals vs. plants) and type of invaded landscape (i.e. urban vs. nonurban) might influence public perception about the management of invasive species, and (2) to assess the potential of public awareness to increase public support for invasive species management. We reviewed the scientific literature on the conflicts of interest around the management of alien species and administered two-phased questionnaires (before and after providing information on the target species and its management) to members of the public in South Africa and the UK (n = 240). Our review suggests that lack of public support for the management of invasive animals in both urban and non-urban areas derives mainly from moralistic value disagreements, while the management of invasive plants in non-urban areas mostly causes conflicts based on utilitarian value disagreements. Despite these general trends, conflicts are context dependent and can originate from a wide variety of different views. Notably, informing the public about the invasive status and negative impacts of the species targeted for management appeared to increase public support for the management actions. Therefore, our results align with the view that increased public awareness might increase the public support for the management of invasive species, independent of taxonomic position and type of landscape

Validation and psychometric analysis of the Internet Addiction Test in Spanish among college students

BACKGROUND: The wide use of the Internet in the workplace, academic or social field, can have an impact on daily life. One of the most used questionnaires worldwide to analyse these problems is the Internet Addiction Test (IAT). Our aim was to validate a Spanish version of the IAT and analyse its psychometric properties. METHODS: Population of study were college students participating in the uniHcos project (Universities of Granada, Huelva, Jaén, León, Salamanca, and Vigo). The questionnaire was translated and back-translated by two native English speakers. Reliability of scores was analysed using Pearson's correlation coefficient and agreement was analysed using the Bland-Altman and Kappa techniques. Test dimensions were analysed by exploratory and confirmatory factor analysis. RESULTS: The reliability of scores was good (r = 0.899, Kappa = 0.650 and mean difference using Bland-Altman = -3.5). The psychometric assessment identified two factors (Emotional Investment; Performance and Time Management) which explained 55 % of the variance (total internal consistency of 0.91) and only 19 items. The confirmatory analysis showed an acceptable goodness of fit, especially when items 6 and 8 were related (RMSEA = 0.07 90%IC = 0.06 - 0.08; WRMR = 1.01, CFI = 0.96; TLI = 0.95). The two dimensions were negatively correlated with age and positively correlated with time spent online, especially for the purposes of leisure and entertainment. DISCUSSION: The results show good reliability and psychometric properties of the Spanish version of IAT with a two-dimensional solution. This result is partially in concordance with previous validations of the IAT in other languages that have found uni- and multi-dimensional solutions using different methodologies. Moreover, we want to highlight the possibility that some item of this questionnaire is outdated due to the technological and lifestyles changes and should be not taken into account. CONCLUSION: The reliability and psychometric properties obtained in this study support the conclusion that this Spanish short version of the IAT represents a useful tool for the analysis of problems arising from misuse of the Internet

New Insights into the Apoptotic Process in Mollusks: Characterization of Caspase Genes in Mytilus galloprovincialis

Apoptosis is an essential biological process in the development and maintenance of immune system homeostasis. Caspase proteins constitute the core of the apoptotic machinery and can be categorized as either initiators or effectors of apoptosis. Although the genes encoding caspase proteins have been described in vertebrates and in almost all invertebrate phyla, there are few reports describing the initiator and executioner caspases or the modulation of their expression by different stimuli in different apoptotic pathways in bivalves. In the present work, we characterized two initiator and four executioner caspases in the mussel Mytilus galloprovincialis. Both initiators and executioners showed structural features that make them different from other caspase proteins already described. Evaluation of the genes’ tissue expression patterns revealed extremely high expression levels within the gland and gills, where the apoptotic process is highly active due to the clearance of damaged cells. Hemocytes also showed high expression values, probably due to of the role of apoptosis in the defense against pathogens. To understand the mechanisms of caspase gene regulation, hemocytes were treated with UV-light, environmental pollutants and pathogen-associated molecular patterns (PAMPs) and apoptosis was evaluated by microscopy, flow cytometry and qPCR techniques. Our results suggest that the apoptotic process could be tightly regulated in bivalve mollusks by overexpression/suppression of caspase genes; additionally, there is evidence of caspase-specific responses to pathogens and pollutants. The apoptotic process in mollusks has a similar complexity to that of vertebrates, but presents unique features that may be related to recurrent exposure to environmental changes, pollutants and pathogens imposed by their sedentary nature

Identification of CIITA Regulated Genetic Module Dedicated for Antigen Presentation

The class II trans-activator CIITA is a transcriptional co-activator required for the expression of Major Histocompatibility Complex (MHC) genes. Although the latter function is well established, the global target-gene specificity of CIITA had not been defined. We therefore generated a comprehensive list of its target genes by performing genome-wide scans employing four different approaches designed to identify promoters that are occupied by CIITA in two key antigen presenting cells, B cells and dendritic cells. Surprisingly, in addition to MHC genes, only nine new targets were identified and validated by extensive functional and expression analysis. Seven of these genes are known or likely to function in processes contributing to MHC-mediated antigen presentation. The remaining two are of unknown function. CIITA is thus uniquely dedicated for genes implicated in antigen presentation. The finding that CIITA regulates such a highly focused gene expression module sets it apart from all other transcription factors, for which large-scale binding-site mapping has indicated that they exert pleiotropic functions and regulate large numbers of genes

Predicting the Electron Requirement for Carbon Fixation in Seas and Oceans

Marine phytoplankton account for about 50% of all global net primary productivity (NPP). Active fluorometry, mainly Fast Repetition Rate fluorometry (FRRf), has been advocated as means of providing high resolution estimates of NPP. However, not measuring CO2-fixation directly, FRRf instead provides photosynthetic quantum efficiency estimates from which electron transfer rates (ETR) and ultimately CO2-fixation rates can be derived. Consequently, conversions of ETRs to CO2-fixation requires knowledge of the electron requirement for carbon fixation (Φe,C, ETR/CO2 uptake rate) and its dependence on environmental gradients. Such knowledge is critical for large scale implementation of active fluorescence to better characterise CO2-uptake. Here we examine the variability of experimentally determined Φe,C values in relation to key environmental variables with the aim of developing new working algorithms for the calculation of Φe,C from environmental variables. Coincident FRRf and 14C-uptake and environmental data from 14 studies covering 12 marine regions were analysed via a meta-analytical, non-parametric, multivariate approach. Combining all studies, Φe,C varied between 1.15 and 54.2 mol e- (mol C)-1 with a mean of 10.9±6.91 mol e- mol C)-1. Although variability of Φe,C was related to environmental gradients at global scales, region-specific analyses provided far improved predictive capability. However, use of regional Φe,C algorithms requires objective means of defining regions of interest, which remains challenging. Considering individual studies and specific small-scale regions, temperature, nutrient and light availability were correlated with Φe,C albeit to varying degrees and depending on the study/region and the composition of the extant phytoplankton community. At the level of large biogeographic regions and distinct water masses, Φe,C was related to nutrient availability, chlorophyll, as well as temperature and/or salinity in most regions, while light availability was also important in Baltic Sea and shelf waters. The novel Φe,C algorithms provide a major step forward for widespread fluorometry-based NPP estimates and highlight the need for further studying the natural variability of Φe,C to verify and develop algorithms with improved accuracy. © 2013 Lawrenz et al