In vitro effects of resistin on epithelial to mesenchymal transition (EMT) in MCF-7 and MDA-MB-231 breast cancer cells - qRT-PCR and Westen blot analyses data.

Resistin is an adipokine produced by the white adipocytes and adipose-derived macrophages, which mediates inflammation and insulin resistance Huang et al., 1997 and Renehan et al., 2008 Feb. Here, we provide data on the effect of resistin on epithelial to mesenchymal transition (EMT) in breast cancer cells in vitro. As model systems, we used human MCF-7 (low-metastatic) and MDA-MB-231 (high-metastatic) breast cancer cell lines. To optimize experimental conditions, we treated the cells with various concentrations of resistin (12.5, 25 and 50 ng/ml) for different time intervals (6 and 24 hours), and measured SOCS3 mRNA expression by using qRT-PCR analysis. Further, we used qRT-PCR and Western blot analyses to measure the expression of various epithelial (E-cadherin, claudin-1) and mesenchymal (SNAIL, SLUG, ZEB1, TWIST1, fibronectin, and vimentin) markers after resistin treatment. This data article is part of a study Avtanski et al., 2019 May, where detailed interpretation and discussion can be found

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

Anchoring Bias in Online Voting

Voting online with explicit ratings could largely reflect people's preferences and objects' qualities, but ratings are always irrational, because they may be affected by many unpredictable factors like mood, weather, as well as other people's votes. By analyzing two real systems, this paper reveals a systematic bias embedding in the individual decision-making processes, namely people tend to give a low rating after a low rating, as well as a high rating following a high rating. This so-called \emph{anchoring bias} is validated via extensive comparisons with null models, and numerically speaking, the extent of bias decays with interval voting number in a logarithmic form. Our findings could be applied in the design of recommender systems and considered as important complementary materials to previous knowledge about anchoring effects on financial trades, performance judgements, auctions, and so on.Comment: 5 pages, 4 tables, 5 figure

Societal sentience: constructions of the public in animal research policy and practice

The use of non-human animals as models in research and drug testing is a key route through which contemporary scientific knowledge is certified. Given ethical concerns, regulation of animal research promotes the use of less ‘sentient’ animals. This paper draws on a documentary analysis of legal documents, and qualitative interviews with Named Veterinary Surgeons and others at a commercial laboratory in the UK. Its key claim is that the concept of animal sentience is entangled with a particular imaginary of how the general public or wider society views animals. We call this imaginary societal sentience. Against a backdrop of increasing ethnographic work on care encounters in the laboratory, this concept helps to stress the wider context within which such encounters take place. We conclude that societal sentience has potential purchase beyond the animal research field, in helping to highlight the affective dimension of public imaginaries (Welsh and Wynne 2013), and their ethical consequences. Researching and critiquing societal sentience, we argue, may ultimately have more impact on the fate of humans and non-humans in the laboratory, than focusing wholly on ethics as situated practice

Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>(pneumococcus) causes a wide range of clinical manifestations that together constitute a major burden of disease worldwide. The main route of pneumococcal transmission is through asymptomatic colonisation of the nasopharynx. Studies of transmission are currently of general interest because of the impact of the new conjugate-polysaccharide vaccines on nasopharyngeal colonisation (carriage). Here we report the first longitudinal study of pneumococcal carriage that records serotype specific exposure to pneumococci simultaneously within the two most important mixing groups, families and day care facilities.</p> <p>Methods</p> <p>We followed attendees (N = 59) with their family members (N = 117) and the employees (N = 37) in three Finnish day care centres for 9 months with monthly sampling of nasopharyngeal carriage. Pneumococci were cultured, identified and serotyped by standard methods.</p> <p>Results</p> <p>Children in day care constitute a core group of pneumococcal carriage: of the 36 acquisitions of carriage with documented exposure to homologous pneumococci, the attendee had been exposed in her/his day care centre in 35 cases and in the family in 9 cases. Day care children introduce pneumococci to the family: 66% of acquisitions of a new serotype in a family were associated with simultaneous or previous carriage of the same type in the child attending day care. Consequently, pneumococcal transmission was found to take place as micro-epidemics driven by the day care centres. Each of the three day care centres was dominated by a serotype of its own, accounting for 100% of the isolates of that serotype among all samples from the day care attendees.</p> <p>Conclusion</p> <p>The transmission of pneumococci is more intense within than across clusters defined by day care facilities. The ensuing micro-epidemic behaviour enhances pneumococcal transmission.</p

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

<p>Abstract</p> <p>Background</p> <p>Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage.</p> <p>Methods</p> <p>Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0.</p> <p><b>Results</b></p> <p>At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P < 0.05). Cerebrospinal fluid Electron Paramagnetic Resonance signal of nitric oxide was increased in patients against controls. Severe stroke group had an elevated Electron Paramagnetic Resonance signal of lipoperoxiradical compared to less severe stroke. Cerebrospinal fluid nitrate levels in less severe stroke patients were higher than those for severe stroke and control. Positive correlation was established between the initial interleukin-6 content and ischemic lesion size as well as with National Institute Health Stroke Scale score on the seventh day. Initial interleukin-6 and nitrate levels in cerebrospinal fluid found to be significant for functional outcome of stroke at one month.</p> <p><b>Conclusion</b></p> <p>According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.</p

Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study

Background: Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. Methods: We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model. Findings: The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period. Interpretation: Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design. Funding: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.Fil: Lo, Stephanie W.. Wellcome Sanger Institute; Reino UnidoFil: Gladstone, Rebecca A.. Wellcome Sanger Institute; Reino UnidoFil: van Tonder, Andries J.. Wellcome Sanger Institute; Reino UnidoFil: Lees, John A.. University Of New York. School Of Medicine; Estados UnidosFil: du Plessis, Mignon. National Institute For Communicable Diseases; SudáfricaFil: Benisty, Rachel. Ben Gurion University of the Negev; IsraelFil: Givon Lavi, Noga. Ben Gurion University of the Negev; IsraelFil: Hawkins, Paulina A.. University of Emory. Rollins School of Public Health; Estados UnidosFil: Cornick, Jennifer E.. Malawi liverpool wellcome trust; MalauiFil: Kwambana Adams, Brenda. University College London; Estados UnidosFil: Law, Pierra Y.. University of Hong Kong; ChinaFil: Ho, Pak Leung. University of Hong Kong; ChinaFil: Antonio, Martin. Medical Research Council Unit The Gambia; GambiaFil: Everett, Dean B.. University of Edinburgh; Reino UnidoFil: Dagan, Ron. Ben Gurion University of the Negev; IsraelFil: Von Gottberg, Anne. National Institute For Communicable Diseases; SudáfricaFil: Klugman, Keith P.. University of Emory. Rollins School of Public Health; Estados UnidosFil: McGee, Lesley. Centers for Disease Control and Prevention; Estados UnidosFil: Breiman, Robert F.. University of Emory. Rollins School of Public Health; Estados UnidosFil: Bentley, Stephen D.. Wellcome Sanger Institute; Reino UnidoFil: Brooks, Abdullah W.. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Corso, Alejandra. The Global Pneumococcal Sequencing Consortium; Reino Unido. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; ArgentinaFil: Davydov, Alexander. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Maguire, Alison. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Pollard, Andrew. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Kiran, Anmol. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Skoczynska, Anna. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Moiane, Benild. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Beall, Bernard. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Sigauque, Betuel. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Aanensen, David. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Lehmann, Deborah. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Faccone, Diego Francisco. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Multi-method Analysis of Avian Eggs as Grave Goods: Revealing Symbolism in Conversion Period Burials at Kukruse, NE Estonia

Eggshells are unusual finds in the Iron Age of eastern Europe (500 BC–1200 AD) deserving extra attention in terms of analysis as well as interpretation. This paper discusses two rare eggshell finds, discovered in female burials at the conversion period (12th–13th century AD) cemetery at Kukruse, NE Estonia. Our multianalytical study combining FT-IR, SEM(-EDS), microscopy and ZooMS provides an overview of methods applicable for identifying egg species, their predepositional history and curation. Based on the analytical results and the comparative analysis of the content and context of these two burials, we argue that different aims and connotations lay behind depositing eggs as burial goods, allowing well-supported interpretations of both pagan and Christian religious worldviews simultaneously