Delineating Genetic Alterations for Tumor Progression in the MCF10A Series of Breast Cancer Cell Lines

To gain insight into the role of genomic alterations in breast cancer progression, we conducted a comprehensive genetic characterization of a series of four cell lines derived from MCF10A. MCF10A is an immortalized mammary epithelial cell line (MEC); MCF10AT is a premalignant cell line generated from MCF10A by transformation with an activated HRAS gene; MCF10CA1h and MCF10CA1a, both derived from MCF10AT xenografts, form well-differentiated and poorly-differentiated malignant tumors in the xenograft models, respectively. We analyzed DNA copy number variation using the Affymetrix 500 K SNP arrays with the goal of identifying gene-specific amplification and deletion events. In addition to a previously noted deletion in the CDKN2A locus, our studies identified MYC amplification in all four cell lines. Additionally, we found intragenic deletions in several genes, including LRP1B in MCF10CA1h and MCF10CA1a, FHIT and CDH13 in MCF10CA1h, and RUNX1 in MCF10CA1a. We confirmed the deletion of RUNX1 in MCF10CA1a by DNA and RNA analyses, as well as the absence of the RUNX1 protein in that cell line. Furthermore, we found that RUNX1 expression was reduced in high-grade primary breast tumors compared to low/mid-grade tumors. Mutational analysis identified an activating PIK3CA mutation, H1047R, in MCF10CA1h and MCF10CA1a, which correlates with an increase of AKT1 phosphorylation at Ser473 and Thr308. Furthermore, we showed increased expression levels for genes located in the genomic regions with copy number gain. Thus, our genetic analyses have uncovered sequential molecular events that delineate breast tumor progression. These events include CDKN2A deletion and MYC amplification in immortalization, HRAS activation in transformation, PIK3CA activation in the formation of malignant tumors, and RUNX1 deletion associated with poorly-differentiated malignant tumors

Detecting Mediterranean White Sharks with Environmental DNA

The white shark (Carcharodon carcharias) is a globally distributed, ecologically important top predator whose biology and population dynamics are challenging to study. Basic biological parameters remain virtually unknown in the Mediterranean Sea due to its historically low population density, dwindling population size, and lack of substantial sightings. White sharks are considered Critically Endangered in the Mediterranean Sea, and recent analyses suggest that the population has declined by 52% to 96% from historical levels in different Mediterranean sectors (Moro et al., 2020). Thus, white shark sightings dating back to 1860 are being used to estimate population trajectories throughout the entire region. Though the population size is unknown, remaining individuals are thought to be primarily restricted to a handful of hotspots deemed important for their reproduction and foraging. One of these hypothesized hotspots is the Sicilian Channel, which accounts for 19% of total historical sightings

Boris Havel, Pregled povijesti Izraela. Od Abrahama do moderne države, Zagreb, Antibarbarus, 2015, 308 str.

Long-term monitoring of seabird numbers around Antarctica has revealed that the chinstrap penguin (Pygoscelis antarctica) is largely declining throughout its range in the Scotia Arc. Whether archipelagos across this large area remain connected via dispersal or represent genetically isolated groups has not yet been established. The purpose of this study was to assess the level of genetic differentiation between four breeding colonies on the Western Antarctic Peninsula (WAP), South Shetland, South Orkney, and South Sandwich Islands using microsatellite-based analysis of population structure. All colonies had similar levels of genetic diversity (mean heterozygosity, H O = 0.583) but colonies from the WAP and South Orkney Island had significant inbreeding coefficients. Hierarchical and pairwise F-statistics revealed very limited population structure in the Scotia Arc, with weak differentiation between colonies from the WAP, South Shetland and South Orkney Islands relative to the South Sandwich Islands, which are situated at least 1000 km apart from these other archipelagos. Bayesian model-based clustering methods found no evidence of significant population structuring, suggesting that whilst some isolation by distance may occur, there are no strong barriers to dispersal across this wide geographic range. No evidence of sex-biased dispersal was detected. We conclude that chinstrap penguin colonies across the Scotia Arc represent one interconnected breeding population. High levels of gene flow may be important in maintaining smaller, less stable colonies, and this status should be preserved by creating dispersal corridors throughout the Scotia Arc

Predictive Value Tools as an Aid in Chemopreventive Agent Development

Over 25 years, the National Cancer Institute’s Division of Cancer Prevention has entered some 800 agents into a chemopreventive agent testing program. Two critical steps involve: 1) in vitro/in vivo morphologic assays and 2) animal tumor assays (incidence/multiplicity reduction). We sought to determine how accurately the earlier-stage (morphologic) assays predict efficacy in the later-stage (animal tumor) assays

Identifying and managing patients at risk of severe allergic reactions to food: report from two iFAAM workshops

Food allergy affects a small but important number of children and adults. Much of the morbidity associated with food allergy is driven by the fear of a severe reaction, and fatalities continue to occur. Foods are the commonest cause of anaphylaxis. One of the aims of the European Union funded Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) project was to improve the identification and management of children and adults at risk of experiencing a severe reaction. A number of interconnected studies within the project have focused on quantifying the severity of allergic reactions; the impact of food matrix, immunological factors on severity of reactions; the impact of co‐factors such as medications on the severity of reactions; utilising single dose challenges to understand threshold and severity of reactions; and community studies to understand the experience of patients suffering real‐life allergic reactions to food. Associated studies have examined population thresholds, and co‐factors such as exercise and stress. This paper summarises two workshops focused on the severity of allergic reactions to food. It outlines the related studies being undertaken in the project indicating how they are likely to impact on our ability to identify individuals at risk of severe reactions and improve their management

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

Motivational Interviewing as an intervention to increase adolescent self-efficacy and promote weight loss: Methodology and design

<p>Abstract</p> <p>Background</p> <p>Childhood obesity is associated with serious physiological and psychological consequences including type 2 diabetes, higher rates of depression and low self-esteem. With the population of overweight and obese youth increasing, appropriate interventions are needed that speak to the issue of readiness to change and motivation to maintain adherence to healthy behavior changes. Motivational Interviewing (MI) is a method of therapy found to resolve ambivalence, enhance intrinsic motivation and promote confidence in a person's ability to make behavior changes. While MI has shown promise in the adult obesity literature as effecting positive lifestyle change, little is known about the effectiveness of MI with overweight and obese youth. This study aims to: 1) demonstrate that MI is an effective intervention for increasing a person's self-efficacy; 2) demonstrate that exposure to MI will facilitate healthy behavior changes; 3) explore psychological changes related to participation in MI and 4) compare physiological and anthropometric outcomes before and after intervention.</p> <p>Methods/Design</p> <p>The current investigation is a prospective study conducted with ongoing participants who regularly attend an outpatient pediatric care center for weight-loss. Overweight youth (BMI > 85^th%ile) between the ages of 10 and 18 who meet eligibility criteria will be recruited. Participants will be randomly assigned to a control group (social skills training) or a treatment group (MI). Participants will meet with the therapist for approximately 30 minutes prior to seeing the dietician, over the course of 6 months. Participants will also undergo a full day assessment at the beginning and end of psychology intervention to evaluate body fat, and metabolic risk (screening for diabetes, high cholesterol, high blood pressure and fitness level). The paper and pencil portions of the assessments as well as the clinical testing will occur at baseline and at the conclusion of the intervention (6 months) with a repeat assessment 6 months following the completion of the intervention.</p> <p>Discussion</p> <p>Results from this study are expected to enhance our understanding of the efficacy of MI with children and adolescents who are overweight or obese.</p> <p>Trial registration</p> <p>Current Controlled Trials #<a href="http://www.clinicaltrials.gov/ct2/show/NCT00326404">NCT00326404</a>.</p

Influence of Genetic Background and Tissue Types on Global DNA Methylation Patterns

Recent studies have shown a genetic influence on gene expression variation, chromatin, and DNA methylation. However, the effects of genetic background and tissue types on DNA methylation at the genome-wide level have not been characterized extensively. To study the effect of genetic background and tissue types on global DNA methylation, we performed DNA methylation analysis using the Affymetrix 500K SNP array on tumor, adjacent normal tissue, and blood DNA from 30 patients with esophageal squamous cell carcinoma (ESCC). The use of multiple tissues from 30 individuals allowed us to evaluate variation of DNA methylation states across tissues and individuals. Our results demonstrate that blood and esophageal tissues shared similar DNA methylation patterns within the same individual, suggesting an influence of genetic background on DNA methylation. Furthermore, we showed that tissue types are important contributors of DNA methylation states

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The Mediterranean diet for Polish infants: a losing struggle or a battle still worth fighting?

The Mediterranean diet is well known for its health-promoting effects. Among its key ingredients, olive oil is the most characteristic. Processing industries have been successfully manufacturing and marketing jarred baby foods with the use of vegetable oils, including olive oil, as well as other sources of visible fat. We aimed to survey manufacturer claims concerning added fat in jarred infant foods supplied to the Polish market. A total of 124 kinds of infant foods from six suppliers were analyzed. Corn, canola, and soybean oil occupied the first three positions, respectively, in rank order of vegetable oils used in jarred baby foods. In our sample, only one type of ready-to-eat jars with vegetables contained olive oil. 11% of products contained cow milk butter or cream. 61% of jarred “dinners” contained poultry or fish, which are typical sources of animal protein in the Mediterranean diet. Given that commercial baby foods currently available in the Polish market contain no olive oil, we advocate considering home preparation of infant foods with the use of visible fat. Medical professionals should encourage food manufacturers to return to the concepts of the Mediterranean diet for young consumers, aimed at long-term health