RKIP Suppresses Breast Cancer Metastasis to the Bone by Regulating Stroma-Associated Genes

In the past decade cancer research has recognized the importance of tumorstroma interactions for the progression of primary tumors to an aggressive and invasive phenotype and for colonization of new organs in the context of metastasis. The dialogue between tumor cells and the surrounding stroma is a complex and dynamic phenomenon, as many cell types and soluble factors are involved. While the function of many of the players involved in this cross talk have been studied, the regulatory mechanisms and signaling pathways that control their expression haven't been investigated in depth. By using a novel, interdisciplinary approach applied to the mechanism of action of the metastasis suppressor, Raf kinase inhibitory protein (RKIP), we identified a signaling pathway that suppresses invasion and metastasis through regulation of stroma-associated genes. Conceptually, the approach we developed uses a master regulator and expression arrays from breast cancer patients to formulate hypotheses based on clinical data. Experimental validation is followed by further bioinformatic analysis to establish the clinical significance of discoveries. Using RKIP as an example we show here that this multi-step approach can be used to identify gene regulatory mechanisms that affect tumor-stroma interactions that in turn influence metastasis to the bone or other organs

Deducing in Vivo Toxicity of Combustion-Derived Nanoparticles from a Cell-Free Oxidative Potency Assay and Metabolic Activation of Organic Compounds

BACKGROUND: The inhalation of combustion-derived nanoparticles (CDNPs) is believed to cause an oxidative stress response, which in turn may lead to pulmonary or even systemic inflammation. OBJECTIVE AND METHODS: In this study we assessed whether the in vivo inflammatory response-which is generally referred to as particle toxicity-of mice to CDNPs can be predicted in vitro by a cell-free ascorbate test for the surface reactivity or, more precisely, oxidative potency (Ox(Pot),) of particles. RESULTS: For six types of CDNPs with widely varying particle diameter (10-50 nm), organic content (OC; 1-20%), and specific Brunauer, Emmett, and Teller (BET) surface area (43-800 m(2)/g), Ox(Pot) correlated strongly with the in vivo inflammatory response (pulmonary polymorphonuclear neutrophil influx 24 hr after intratracheal particle instillation). However, for CDNPs with high organic content, Ox(Pot) could not explain the observed inflammatory response, possibly due to shielding of the Ox(Pot) of the carbon core of CDNPs by an organic coating. On the other hand, a pathway-specific gene expression screen indicated that, for particles rich in polycyclic aromatic hydrocarbon (PAHs), cytochrome P450 1A1 (CYP1A1) enzyme-mediated biotransformation of bioavailable organics may generate oxidative stress and thus enhance the in vivo inflammatory response. CONCLUSION: The compensatory nature of both effects (shielding of carbon core and biotransformation of PAHs) results in a good correlation between inflammatory response and BET surface area for all CDNPs. Hence, the in vivo inflammatory response can either be predicted by BET surface area or by a simple quantitative model, based on in vitro Ox(Pot) and Cyp1a1 induction

International Trends and Practices on Sustainability Reporting in Higher Education Institutions

Sustainability reports are regarded as important tools in offering information about the environmental, social, economic, and institutional performance of an institution, and in demonstrating a commitment to matters related to sustainable development. But even though sustainability reporting has been used by a variety of higher education institutions to date, it is not as widely practiced as it should be. To further investigate this topic, a twofold approach was used: a study focusing on sustainability reporting approaches deployed in a sample of 30 universities across a set of countries; and a survey with a sample of 72 universities from different global regions to assess the extent to which they are deploying sustainability reporting as part of their activities. The scientific value of the paper resides in the fact that it offers a comprehensive overview of the subject matter of sustainability reporting, and how higher education institutions handle it. It also outlines the efforts in developing these documents which may catalyse further progress in this key area

Gender-specific differences in COPD symptoms and their impact for the diagnosis of cardiac comorbidities

Background In chronic obstructive pulmonary disease (COPD), gender-specifc diferences in the prevalence of symptoms and comorbidity are known. Research question We studied whether the relationship between these characteristics depended on gender and carried diag nostic information regarding cardiac comorbidities. Study design and methods The analysis was based on 2046 patients (GOLD grades 1–4, 795 women; 38.8%) from the COSYCONET COPD cohort. Assessments comprised the determination of clinical history, comorbidities, lung function, COPD Assessment Test (CAT) and modifed Medical Research Council dyspnea scale (mMRC). Using multivariate regres sion analyses, gender-specifc diferences in the relationship between symptoms, single CAT items, comorbidities and functional alterations were determined. To reveal the relationship to cardiac disease (myocardial infarction, or heart failure, or coronary artery disease) logistic regression analysis was performed separately in men and women. Results Most functional parameters and comorbidities, as well as CAT items 1 (cough), 2 (phlegm) and 5 (activities), dif fered signifcantly (p<0.05) between men and women. Beyond this, the relationship between functional parameters and comorbidities versus symptoms showed gender-specifc diferences, especially for single CAT items. In men, item 8 (energy), mMRC, smoking status, BMI, age and spirometric lung function was related to cardiac disease, while in women primarily age was predictive. Interpretation Gender-specifc diferences in COPD not only comprised diferences in symptoms, comorbidities and func tional alterations, but also diferences in their mutual relationships. This was refected in diferent determinants linked to cardiac disease, thereby indicating that simple diagnostic information might be used diferently in men and women. Clinical trial registration The cohort study is registered on ClinicalTrials.gov with identifer NCT01245933 and on Ger manCTR.de with identifer DRKS00000284, date of registration November 23, 2010. Further information can be obtained on the website http://www.asconet.net

Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment

We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging efects of metformin. Patients of GOLD grades 1–4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO difusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulflled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was signifcantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p < 0.05 each), but not the decline of FEV1 and FVC. These results were confrmed using multiple regression and propensity score analyses. Our fndings demonstrate an association between the annual decline of lung difusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging efects of metformin as refected in a surrogate marker of emphysema

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

Best clinical practice guidance for treating deep carious lesions in primary teeth: an EAPD policy document.

PURPOSE The European Academy of Paediatric Dentistry (EAPD) has developed this best clinical practice guidance to help clinicians manage deep carious lesions in primary teeth. METHODS Three expert groups conducted systematic reviews of the relevant literature. The topics were: (1) conventional techniques (2) Minimal Intervention Dentistry (MID) and (3) materials. Workshops were held during the corresponding EAPD interim seminar in Oslo in April 2021. Several clinical based recommendations and statements were agreed upon, and gaps in our knowledge were identified. RESULTS There is strong evidence that indirect pulp capping and pulpotomy techniques, and 38% Silver Diamine Fluoride are shown to be effective for the management of caries in the primary dentition. Due to the strict criteria, it is not possible to give clear recommendations on which materials are most appropriate for restoring primary teeth with deep carious lesions. Atraumatic Restorative Technique (ART) is not suitable for multi-surface caries, and Pre-formed Metal Crowns (PMCs) using the Hall technique reduce patient discomfort. GIC and RMGIC seem to be more favourable given the lower annual failure rate compared to HVGIC and MRGIC. Glass carbomer cannot be recommended due to inferior marginal adaptation and fractures. Compomers, hybrid composite resins and bulk-fill composite resins demonstrated similar values for annual failure rates. CONCLUSION The management of deep carious lesions in primary teeth can be challenging and must consider the patient's compliance, operator skills, materials and costs. There is a clear need to increase the use of MID techniques in managing carious primary teeth as a mainstream rather than a compromise option