Automated rendering of multi-stranded DNA complexes with pseudoknots

We present a general method for rendering representations of multi-stranded DNA complexes from textual descriptions into 2D diagrams. The complexes can be arbitrarily pseudoknotted, and if a planar rendering is possible, the method will determine one in time which is essentially linear in the size of the textual description. (That is, except for a final stochastic fine-tuning step.) If a planar rendering is not possible, the method will compute a visually pleasing approximate rendering in quadratic time. Examples of diagrams produced by the method are presented in the paper.Comment: 12 pages, 7 figure

Expression of galectin-3 in nephrotic syndrome glomerulopaties in children.

BACKGROUNDGalectins are a family of ancient animal carbohydrate binding proteins; the name is from their description as beta-galactoside-specific lectins. They have been strongly implicated in inflammation and cancer. Studies of the association of galectins with various aspects of kidney disease in humans are still at an early stage. In line with the above, the aim of the present report was to analyse the immunohistochemical expression of galectin-3 (the only chimera galectin currently identified) in renal biopsy specimens of children with idiopathic nephrotic syndrome (INS).PATIENTS AND METHODSEighteen children with minimal change disease (MCD), 30 with diffuse mesangial proliferation (DMP) and 11 with focal segmental glomerulosclerosis (FSGS) treated between 2003 and 2006 in the Department of Paediatric Cardiology and Nephrology, Poznan University of Medical Sciences. An indirect immunohistochemical protocol using a polyclonal rabbit antibody against human galectin-3 was employed.RESULTSIn the control, MCD and DMP children who responded to steroid therapy anti-galectin-3 reactivity was present both in renal cortex and medulla. It was the strongest within cortical collecting ducts and subjectively less expressed in distal tubules. The total number of galectin-3 positive cortical and medullary segments of collecting ducts was significantly higher in the subjects who did not respond to steroid therapy These patients revealed also immunohistochemical reactivity of galectin-3 within nuclei of individual glomerular mesangial cells (

High correlation between the turnover of nucleotides under mutational pressure and the DNA composition

BACKGROUND: Any DNA sequence is a result of compromise between the selection and mutation pressures exerted on it during evolution. It is difficult to estimate the relative influence of each of these pressures on the rate of accumulation of substitutions. However, it is important to discriminate between the effect of mutations, and the effect of selection, when studying the phylogenic relations between taxa. RESULTS: We have tested in computer simulations, and analytically, the available substitution matrices for many genomes, and we have found that DNA strands in equilibrium under mutational pressure have unique feature: the fraction of each type of nucleotide is linearly dependent on the time needed for substitution of half of nucleotides of a given type, with a correlation coefficient close to 1. Substitution matrices found for sequences under selection pressure do not have this property. A substitution matrix for the leading strand of the Borrelia burgdorferi genome, having reached equilibrium in computer simulation, gives a DNA sequence with nucleotide composition and asymmetry corresponding precisely to the third positions in codons of protein coding genes located on the leading strand. CONCLUSIONS: Parameters of mutational pressure allow us to count DNA composition in equilibrium with this mutational pressure. Comparing any real DNA sequence with the sequence in equilibrium it is possible to estimate the distance between these sequences, which could be used as a measure of the selection pressure. Furthermore, the parameters of the mutational pressure enable direct estimation of the relative mutation rates in any DNA sequence in the studied genome

Prevalence of estrogen receptor alpha PvuII and XbaI polymorphism in population of Polish postmenopausal women.

Numerous data indicate that polymorphism of estrogen receptor alpha (ERalpha) may predict lipid levels, lipid response to hormone replacement therapy (HRT), myocardial infarction risk, bone fracture risk, bone mineral density (BMD) and changes in BMD over time. In this study we aimed to evaluate distribution of ERalpha PvuII and XbaI genotypes in population of Polish postmenopausal women qualified to different protocols of HRT. Subject of the study were 64 consecutive postmenopausal women aged from 45 to 65 years (mean 56.6) assigned to HRT. ERalpha PvuII and XbaI polymorphism was determined by PCR-restriction fragment length polymorphism (RFLP). The absence of PvuII and XbaI restriction sites were indicated by "P" and "X" and presence by "p" and "x", respectively. PvuII genotype was distributed as follows: PP 17.2% (n=11), Pp 50% (n=32), pp 32.83% (n=21). Frequency of XbaI genotype was: XX 6.25% (n=4), Xx 34.4% (n=22), xx 59.4% (n=38). Four haplotypes with following frequencies were recognized: PX 17.3%, px 47.4%, Px 24.4% and pX 10.9%. Prevalence of estrogen receptor alpha PvuII and XbaI polymorphisms in Polish women is similar to previously studied population

Crisis management and crisis situation in the organization

PURPOSE: The aim of the article is to present the problems of crisis management and crisis situation in an organisation, taking into consideration that crisis is an integral part of the functioning of any organisation.DESIGN/METHODOLOGY/APPROACH: Realisation of the goal indicated will help find an answer to the research problem: How does the occurrence of a crisis affect the functioning of an organisation, particularly in a time of chaos and uncertainty? Qualitative methods were applied to obtain an answer to the research question posed. The research made use of the latest report containing statistics concerning crisis and resilience of organisations, an analysis was also conducted based on both domestic and foreign scientific articles from recent years.FINDINGS: The authors formulated the following conclusions: Crisis is inevitable, but its effects can be mitigated. Organisations which are prepared for a crisis have a greater chance of successfully overcoming it. Crisis management is a complex process requiring the commitment of the entire team. Organisations should conduct regular reviews of their crisis plans to ensure that they have not become outdated and their effectiveness has not decreased. Organisations should also carry out crisis training to test their plans and prepare employees for the event of a crisis.PRACTICAL IMPLICATIONS: Crises may have various intensities and effects. Some may be short lasting and have no significant impact on the working of the organisation. Others may be long-term and lead to serious losses, or even the collapse of a company. In order to minimise the risk of a crisis, organisations should apply the appropriate crisis management strategies. which indicates the necessity to take these into account in the organisation’s practices, in plans and action strategies, stressing the creation of various scenarios for future development.ORIGINALITY/VALUE: An analysis of the materials gathered proves that crises may become a catalyst for change with regard to generating new solutions in the field of coping with crisis situations in an organisation. Particularly noteworthy are organisations in the energy, technology, media and communications sectors, and in the health industry, due to the experience they have in implementing integrated programmes to increase immunity, which may inspire other organisations to take such decisions.peer-reviewe

Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Biomarkers; Triple-negative breast cancerBiomarcadors; Càncer de mama triple negatiuBiomarcadores; Cáncer de mama triple negativoPurpose: Despite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or IHC-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. Experimental Design: In FAIRLANE, 151 patients with early triple-negative breast cancer (TNBC) were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery. Adding ipatasertib did not increase pathologic complete response rate and numerically improved overall response rate by MRI. We used reverse-phase protein microarrays (RPPA) to examine the total level and/or phosphorylation states of over 100 proteins in various signaling or cell processes including PI3K/AKT and mTOR signaling. One hundred and twenty-five baseline and 127 on-treatment samples were evaluable by RPPA, with 110 paired samples at both time points. Results: Tumors with genomic/protein alterations in PIK3CA/AKT1/PTEN were associated with higher levels of AKT phosphorylation. In addition, phosphorylated AKT (pAKT) levels exhibited a significant association with enriched clinical benefit of ipatasertib, and identified patients who received benefit in the absence of PIK3CA/AKT1/PTEN alterations. Ipatasertib treatment led to a downregulation of AKT/mTORC1 signaling, which was more pronounced among the tumors with PIK3CA/AKT1/PTEN alterations or among the responders to the treatment. Conclusions: We showed that the high baseline pAKT levels are associated with the alterations of PI3K/AKT pathway components and enriched benefit of ipatasertib in TNBC.This study was sponsored by F. Hoffmann-La Roche Ltd

Ratio of proliferation markers and HSP90 gene expression as a predictor of pathological complete response in breast cancer neoadjuvant chemotherapy

Introduction. Prediction of response to preoperative breast cancer chemotherapy may offer a substantial optimization of medical management of this disease. The most efficient prediction would be done a priori, before the start of chemotherapy and based on the biological features of patient and tumor. Numerous markers have been proposed but none of them has been applied as a routine. The role of MKI67 and HSP90 expression has been recently suggested to predict treatment sensitivity in HER2-positive breast cancer. The aim of this study was to validate the utility of proliferation based markers (MKI67 and CDK1) and heat shock proteins (namely HSP90) to predict response to chemotherapy in cohort of breast cancer patients treated preoperatively. Material and methods. Ninety-three patients with breast cancer, all females, mean age 42.2 years, among them 32% T1-T2 patients, 49% T3 patients and 13% with T4 tumor stage, 27% N0, 42% N1, 16% N2, 15% N3 were subjected to initial chemotherapy. The majority of patients (86%) received anthracycline and taxane chemotherapy. Among the patients there were 9 individuals with metastatic disease (M1) at initial presentation, and 11 patients were not treated surgically after initial chemotherapy (no sufficient disease response). From 82 patients operated on, 20 patients (24%) showed pathological complete response (pCR), while in 62 patients there was no pCR. 42% of patients were hormone-sensitive HER2-negative, 20% hormone-sensitive HER2-positive, 9% only HER-positive and 29% with triple negative breast cancer. Four gene transcripts (MKI67, cyclin-dependent kinase 1 [CDK1], heat shock proteins HSP90AA1 and HSP- 90AB1) were analyzed in total RNA isolated from single core obtained during preoperative core needle biopsy by quantitative real-time PCR with fluorescent probes (Universal Probe Library, Roche). Results were normalized to the panel of reference genes. Results. There were no statistically significant differences in MKI67 and CDK1 expression between pCR and no pCR groups (p = 0.099 and 0.35, respectively), although the median expression of both genes was slightly higher in pCR group. In contrast, both HSP90AA1 and HSP90AB1 transcripts showed decreased expression in pCR group (medians 0.77 and 0.55) when compared to no p CR group (median 0.86 and 0.73), statistically significant for HSP90AA1 (p = 0.031) and of borderline significance for HSP90AB1 (p = 0.054). The most significant predictor of pCR was the ratio of CDK1 transcript to HSP90AA transcript. This ratio was significantly higher in CR group (median 0.99) than in no CR group (median 0.68, p = 0.0023), and showed a potential diagnostic utility (area under receiver operating characteristic [ROC] curve 0.72). Conclusions. HSP90AA1 and AB1 genes exhibit low expression in breast cancers highly sensitive to chemotherapy and may indicate the patients with higher probability of pathological complete response. The ratio of HSP90AA1 to proliferation-related markers (CDK1 or MKI67) may be even better predictor of pCR chance, with higher expression of proliferation genes and lower stress response in patients sensitive to chemotherapy

Highlights from the SOAP project survey. What Scientists Think about Open Access Publishing

The SOAP (Study of Open Access Publishing) project has run a large-scale survey of the attitudes of researchers on, and the experiences with, open access publishing. Around forty thousands answers were collected across disciplines and around the world, showing an overwhelming support for the idea of open access, while highlighting funding and (perceived) quality as the main barriers to publishing in open access journals. This article serves as an introduction to the survey and presents this and other highlights from a preliminary analysis of the survey responses. To allow a maximal re-use of the information collected by this survey, the data are hereby released under a CC0 waiver, so to allow libraries, publishers, funding agencies and academics to further analyse risks and opportunities, drivers and barriers, in the transition to open access publishing.Comment: Data manual available at http://bit.ly/gI8nct Compressed CSV data file available at http://bit.ly/gSmm71 Alternative data formats: CSV http://bit.ly/ejuvKO XLS http://bit.ly/e6gE7o XLSX http://bit.ly/gTjyv

CyTOF workflow: differential discovery in high-throughput high-dimensional cytometry datasets [version 3; peer review: 2 approved]

High-dimensional mass and flow cytometry (HDCyto) experiments have become a method of choice for high-throughput interrogation and characterization of cell populations. Here, we present an updated R-based pipeline for differential analyses of HDCyto data, largely based on Bioconductor packages. We computationally define cell populations using FlowSOM clustering, and facilitate an optional but reproducible strategy for manual merging of algorithm-generated clusters. Our workflow offers different analysis paths, including association of cell type abundance with a phenotype or changes in signalling markers within specific subpopulations, or differential analyses of aggregated signals. Importantly, the differential analyses we show are based on regression frameworks where the HDCyto data is the response; thus, we are able to model arbitrary experimental designs, such as those with batch effects, paired designs and so on. In particular, we apply generalized linear mixed models or linear mixed models to analyses of cell population abundance or cell-population-specific analyses of signaling markers, allowing overdispersion in cell count or aggregated signals across samples to be appropriately modeled. To support the formal statistical analyses, we encourage exploratory data analysis at every step, including quality control (e.g., multi-dimensional scaling plots), reporting of clustering results (dimensionality reduction, heatmaps with dendrograms) and differential analyses (e.g., plots of aggregated signals)