Overexpression of the urokinase receptor splice variant uPAR-del4/5 in breast cancer cells affects cell adhesion and invasion in a dose-dependent manner and modulates transcription of tumor-associated genes

mRNA levels of the urokinase receptor splice variant uPAR-del4/5 are associated with prognosis in breast cancer. Its overexpression in cancer cells affects tumor biologically relevant processes. In the present study, individual breast cancer cell clones displaying low vs. high uPAR-del4/5 expression were analyzed demonstrating that uPAR-del4/5 leads to reduced cell adhesion and invasion in a dose-dependent manner. Additionally, matrix metalloproteinase-9 (MMP-9) was found to be strongly upregulated in uPAR-del4/5 overexpressing compared to vector control cells. uPAR-del4/5 may thus play an important role in the regulation of the extracellular proteolytic network and, by this, influence the metastatic potential of breast cancer cells

Decreasing trends of particle number and black carbon mass concentrations at 16 observational sites in Germany from 2009 to 2018

Anthropogenic emissions are dominant contributors to air pollution. Consequently, mitigation policies have been attempted since the 1990s in Europe to reduce pollution by anthropogenic emissions. To evaluate the effectiveness of these mitigation policies, the German Ultrafine Aerosol Network (GUAN) was established in 2008, focusing on black carbon (BC) and sub-micrometre aerosol particles. In this study, long-term trends of atmospheric particle number concentrations (PNCs) and equivalent BC (eBC) mass concentration over a 10-year period (2009-2018) were determined for 16 GUAN sites ranging from roadside to high Alpine environments. Overall, statistically significant decreasing trends are found for most of these parameters and environments in Germany. The annual relative slope of eBC mass concentration varies between-13.1% and-1.7% per year. The slopes of the PNCs vary from-17.2% to-1.7 %,-7.8% to-1.1 %, and-11.1% to-1.2% per year for 10-30, 30-200, and 200-800 nm size ranges, respectively. The reductions in various anthropogenic emissions are found to be the dominant factors responsible for the decreasing trends of eBC mass concentration and PNCs. The diurnal and seasonal variations in the trends clearly show the effects of the mitigation policies for road transport and residential emissions. The influences of other factors such as air masses, precipitation, and temperature were also examined and found to be less important or negligible. This study proves that a combination of emission mitigation policies can effectively improve the air quality on large spatial scales. It also suggests that a long-term aerosol measurement network at multi-type sites is an efficient and necessary tool for evaluating emission mitigation policies. © 2020 Author(s)

Comparisons of high-risk cervical HPV infections in Caribbean and US populations

<p>Abstract</p> <p>Background</p> <p>Disparities in cervical cancer incidence and mortality rates exist among women of African ancestry (African-American, African-Caribbean and African). Persistent cervical infection with Human papillomavirus (HPV) is associated with cervical dysplasia and if untreated, could potentially progress to invasive cervical cancer. Very few studies have been conducted to examine the true prevalence of HPV infection in this population. Comparisons of cervical HPV infection and the type-specific distribution of HPV were performed between cancer-free Caribbean and US women.</p> <p>Results</p> <p>The Caribbean population consisted of 212 women from Tobago and 99 women from Jamaica. The US population tested, consisted of 82 women from Pittsburgh. The majority of the US subjects was Caucasian, 74% (61/82) while 12% (10/82) and 13% (11/82) were African-American or other ethnic groups, respectively. The age-adjusted prevalence of any HPV infection among women from Tobago was 35%, while for Jamaica, it was 81% (p < 0.0001). The age-adjusted prevalence of HPV infection for Caribbean subjects was not statistically significantly different from the US (any HPV: 47% vs. 39%, p > 0.1; high-risk HPVs: 27% vs. 25%, p > 0.1); no difference was observed between US-Blacks and Jamaicans (any HPV: 92% vs. 81%, p > 0.1; high-risk HPV: 50% vs. 53%, p > 0.1). However, US-Whites had a lower age-adjusted prevalence of HPV infections compared to Jamaican subjects (any HPV: 29% vs. 81%, p < 0.0001; high-risk HPV: 20% vs. 53%, p < 0.001). Subjects from Jamaica, Tobago, and US-Blacks had a higher proportion of high-risk HPV infections (Tobago: 20%, Jamaica: 58%, US-Blacks: 40%) compared to US-Whites (15%). Similar observations were made for the presence of infections with multiple high-risk HPV types (Tobago: 12%, Jamaica: 43%, US-Blacks: 30%, US-Whites: 8%). Although we observed similar prevalence of HPV16 infections among Caribbean and US-White women, there was a distinct distribution of high-risk HPV types when comparisons were made between the ethnic groups.</p> <p>Conclusion</p> <p>The higher prevalence of cervical HPV infections and multiple high-risk infections in Caribbean and US-Black women may contribute to the high incidence and prevalence of cervical cancer in these populations. Evaluation of a larger sample size is currently ongoing to confirm the distinct distribution of HPV types between ethnic groups.</p

Challenging behavior in mucopolysaccharidoses types I–III and day-to-day coping strategies: a cross sectional explorative study

Background!#!Challenging behavior represents a core symptom in neuropathological mucopolysaccharidoses (MPS) and puts major strain on affected families. Although multimodal approaches including behavioral strategies to treatment could be valuable, there is lack of research to the effectiveness of specific measures. This explorative, cross-sectional study is aimed at the collection of parental experiences regarding effective day-to-day measures against challenging behavior in MPS and focuses on 4 major research questions: First: What is challenging behavior in MPS? Second: Which strategies are helpful in the day-to-day coping with challenging behavior? Third: How strong is parental acceptance of illness and the disorder's impact on family relationships? Fourth: What are beneficial personal and interfamilial strategies for generally coping with the disorder?!##!Methods!#!A semi structured questionnaire was designed de novo in cooperation with affected families. 37/268 questionnaires were returned (rate: 13.8%), of which 34 (MPS I: n = 8, MPS II: n = 8; MPS III: n = 18) could be included in data analysis in accordance with inclusion criteria. Assessment of challenging symptoms was based on perceived frequency, parent- and child stress. Exploration of possible coping strategies for challenging behavior and general illness-related strain included the evaluation of perceived effectiveness. Questionnaires were completed by patient's relatives and analyzed for strategies to cope with challenging behavior and the disorder's impact. STROBE criteria were respected.!##!Results!#!MPS I was reported to show lower frequency and better perceived manageability of challenging behavior than MPS II and -III. Sleep disturbance, hyperactivity, agitation, aggression and orality seemed relevant symptoms regarding frequency and/or parent stress. Reported measures were manifold, worthwhile approaches against challenging behavior appeared to be aiming at distraction, relief and environmental changes. Medication and non-medication approaches were rated similarly effective. Social exchange, private space and networking with other affected families seemed highly important for personal and interfamilial well-being.!##!Conclusions!#!Multimodal mentoring for affected families could be based on the following equivalent pillars: (1) Medication therapy for challenging behavior including evaluation of cost and benefit (2) Guided implementation and re-evaluation of specific behavioral measures against challenging behavior. (3) Psychosocial support of MPS-families, including options for strengthening parental well-being and family functioning. Trial registration This study was registered at clinicaltrials.gov prior to study start (NCT-Number: NCT03161171, Date: 2017/05/19)

Cultivating Common Ground: Integrating standards-based visual arts, math and literacy in high-poverty urban classrooms

The Framing Student Success: Connecting Rigorous Visual Arts, Math and Literacy Learning experimental demonstration project was designed to develop and test an instructional program integrating high-quality, standards-based instruction in the visual arts, math, and literacy. Developed and implemented by arts-in-education organization Studio in a School (STUDIO), in partnership with the New York City Department of Education, the Framing Student Success curriculum was designed by experienced professional artist instructors collaborating with school-based visual arts, math, and literacy specialists and classroom teachers.  The Framing Student Success curriculum units were designed to make explicit connections between subjects (visual arts and ELA or math), while maintaining the integrity, depth and rigor of instruction in both subject areas. While students were receiving arts-integrated instruction during each of the twelve six-week units, classroom teachers and arts specialists were receiving embedded professional development. Regular cross-site professional development was also provided for teachers, specialists, and school administrators.As a randomized control trial study, the three-year Framing Student Success study provides robust evidence of the potential impacts of an interdisciplinary, arts-integrated curriculum for students growing up in poverty. The mixed-method study assessed the effects of staff professional development and standards-based arts-integrated instruction in three urban, high-poverty elementary schools. Results indicate that rigorous interdisciplinary instruction that links visual arts, literacy, and math skills, and supports cognitive skill development, can increase students’ literacy and math learning while nurturing their art making skills and enhancing their ability to meaningfully reflect on their own work and that of their peers. Qualitative findings suggest that interdisciplinary educator collaborations were critical to project success, and highlight the project’s successful engagement of lower-performing students and students with disabilities. Survey and focus group results suggest that training can build the capacities of teachers, arts specialists, and administrators to implement an interdisciplinary curriculum, providing educators with additional tools to teach engaging, Common Core aligned lessons addressing academic and cognitive competencies

Cultivating Common Ground: Integrating standards-based visual arts, math and literacy in high-poverty urban classrooms

The Framing Student Success: Connecting Rigorous Visual Arts, Math and Literacy Learning experimental demonstration project was designed to develop and test an instructional program integrating high-quality, standards-based instruction in the visual arts, math, and literacy. Developed and implemented by arts-in-education organization Studio in a School (STUDIO), in partnership with the New York City Department of Education, the Framing Student Success curriculum was designed by experienced professional artist instructors collaborating with school-based visual arts, math, and literacy specialists and classroom teachers.  The Framing Student Success curriculum units were designed to make explicit connections between subjects (visual arts and ELA or math), while maintaining the integrity, depth and rigor of instruction in both subject areas. While students were receiving arts-integrated instruction during each of the twelve six-week units, classroom teachers and arts specialists were receiving embedded professional development. Regular cross-site professional development was also provided for teachers, specialists, and school administrators.As a randomized control trial study, the three-year Framing Student Success study provides robust evidence of the potential impacts of an interdisciplinary, arts-integrated curriculum for students growing up in poverty. The mixed-method study assessed the effects of staff professional development and standards-based arts-integrated instruction in three urban, high-poverty elementary schools. Results indicate that rigorous interdisciplinary instruction that links visual arts, literacy, and math skills, and supports cognitive skill development, can increase students’ literacy and math learning while nurturing their art making skills and enhancing their ability to meaningfully reflect on their own work and that of their peers. Qualitative findings suggest that interdisciplinary educator collaborations were critical to project success, and highlight the project’s successful engagement of lower-performing students and students with disabilities. Survey and focus group results suggest that training can build the capacities of teachers, arts specialists, and administrators to implement an interdisciplinary curriculum, providing educators with additional tools to teach engaging, Common Core aligned lessons addressing academic and cognitive competencies

Metabolic resistance to pre-emergence herbicides in grasses

Black-grass (Alopecurus myosuroides Huds.) and rye-grass (Lolium spp) are very competitive grass weeds. During the last decades, they have evolved resistance to post-emergence herbicides, in particular ACCase- and ALS- inhibitors. This requires more complex weed management strategies. To ensure good control of both weeds, pre-emergence treatments become increasingly important. Particularly flufenacet has become a key herbicide for the control of multiple-resistant black-grass and rye-grass. Yet, in some of those populations, reduced flufenacet efficacy start to be observed. In a screening with black-grass and rye-grass populations of worldwide origins, most populations could be controlled with the registered field rate of flufenacet, however differences in the level of flufenacet efficacy were observed and were in correlation with enhanced flufenacet metabolism. This was particularly the case for rye-grass populations. The use of flufenacet in mixtures with diflufenican, particularly in combination with flurtamone or metribuzin or aclonifen, improved the efficacy significantly. In decreased flufenacet sensitive populations, the efficacy of other pre-emergence herbicides like pendimethalin, prosulfocarb, S-metolachlor, dimethenamid-P and pethoxamid, was also significantly decreased whereas other herbicides like pyroxasulfone or diflufenican remained highly active. This decreased efficacy of flufenacet as well as S-metolachlor was associated with higher metabolism involving glutathione-s-transferases. Although differences between populations were sometimes relatively small, best weed management practices (e.g. application of full dose rates and mixtures) should be applied to reduce selection pressure and prevent the development of resistance. This is particularly important as flufenacet is one of the few still active herbicides suitable for the control of multiple-resistant grass weeds. Use of mixtures associated with agronomic solutions in an Integrated Weed Management approach has to be the main approach

Overexpression of the urokinase receptor splice variant uPAR-del4/5 in breast cancer cells affects cell adhesion and invasion in a dose-dependent manner and modulates transcription of tumor-associated genes

mRNA levels of the urokinase receptor splice variant uPAR-del4/5 are associated with prognosis in breast cancer. Its overexpression in cancer cells affects tumor biologically relevant processes. In the present study, individual breast cancer cell clones displaying low vs. high uPAR-del4/5 expression were analyzed demonstrating that uPAR-del4/5 leads to reduced cell adhesion and invasion in a dose-dependent manner. Additionally, matrix metalloproteinase-9 (MMP-9) was found to be strongly upregulated in uPAR-del4/5 overexpressing compared to vector control cells. uPAR-del4/5 may thus play an important role in the regulation of the extracellular proteolytic network and, by this, influence the metastatic potential of breast cancer cells