Impact of ABC transporters in osteosarcoma and ewing’s sarcoma: Which are involved in chemoresistance and which are not?

The ATP-binding cassette (ABC) transporter superfamily consists of several proteins with a wide repertoire of functions. Under physiological conditions, ABC transporters are involved in cellular trafficking of hormones, lipids, ions, xenobiotics, and several other molecules, including a broad spectrum of chemical substrates and chemotherapeutic drugs. In cancers, ABC transporters have been intensely studied over the past decades, mostly for their involvement in the multidrug resistance (MDR) phenotype. This review provides an overview of ABC transporters, both related and unrelated to MDR, which have been studied in osteosarcoma and Ewing’s sarcoma. Since different backbone drugs used in first-line or rescue chemotherapy for these two rare bone sarcomas are substrates of ABC transporters, this review particularly focused on studies that have provided findings that have been either translated to clinical practice or have indicated new candidate therapeutic targets; however, findings obtained from ABC transporters that were not directly involved in drug resistance were also discussed, in order to provide a more complete overview of the biological impacts of these molecules in osteosarcoma and Ewing’s sarcoma. Finally, therapeutic strategies and agents aimed to circumvent ABC-mediated chemoresistance were discussed to provide future perspectives about possible treatment improvements of these neoplasms

Total Synthesis of Asparenydiol by Two Sonogashira Cross-Coupling Reactions Promoted by Supported Pd and Cu Catalysts

Asparenydiol, which is an important natural compound with potential pharmacological activities, was synthesized through two Sonogashira cross-coupling reactions catalyzed by supported Pd and Cu catalysts and by a Mitsunobu etherification. The optimization of the Sonogashira couplings allowed the use of catalysts supported on different matrices with good results in terms of catalytic efficiency and yields

The Ocean Biomolecular Observing Network (OBON)

Ocean life-from viruses to whales-is built from "biomolecules." Biomolecules such as DNA infuse each drop of ocean water, grain of sediment, and breath of ocean air. The Ocean Biomolecular Observing Network (OBON) is developing a global collaboration that will allow science and society to understand ocean life like never before. The program will transform how we sense, harvest, protect, and manage ocean life using molecular techniques, as it faces multiple stresses including pollution, habitat loss, and climate change. It will also help communities detect biological hazards such as harmful algal blooms and pathogens, and be a key component of next-generation ocean observing systems. OBON will encourage continuous standardization and intercalibration of methods and data interoperability to help enhance and future-proof capabilities. OBON's objectives are: 1) to build a coastal-to-open ocean multi-omics biodiversity observing system; 2) to develop and transfer capacity between partners; 3) to enhance marine ecosystem digitization and modelling and 4) to coordinate action on pressing scientific, management, and policy questions

Successful implementation of inquiry-based physiology laboratories in undergraduate major and nonmajor courses. Adv Physiol Educ 32

Casotti G, Rieser-Danner L, Knabb MT. Successful implementation of inquiry-based physiology laboratories in undergraduate major and nonmajor courses. Adv Physiol Educ 32: 286-296, 2008; doi:10.1152/advan.00100.2007.-Recent evidence has demonstrated that inquiry-based physiology laboratories improve students' criticaland analytical-thinking skills. We implemented inquiry-based learning into three physiology courses: Comparative Vertebrate Physiology (majors), Human Physiology (majors), and Human Anatomy and Physiology (nonmajors). The aims of our curricular modifications were to improve the teaching of physiological concepts, teach students the scientific approach, and promote creative and critical thinking. We assessed our modifications using formative (laboratory exams, oral presentations, and laboratory reports) and summative evaluations (surveys, laboratory notebook, and an end of semester project). Students appreciated the freedom offered by the new curriculum and the opportunity to engage in the inquiry process. Results from both forms of evaluation showed a marked improvement due to the curricular revisions. Our analyses indicate an increased confidence in students' ability to formulate questions and hypotheses, design experiments, collect and analyze data, and make conclusions. Thus, we have successfully incorporated inquiry-based laboratories in both major and nonmajor courses. pedagogy; curriculum; evaluation INQUIRY-BASED LEARNING is an alternative pedagogical method of classroom teaching that is characterized by a focus on learning through discovery. It incorporates four approaches to teaching: 1) a focus on ideas and concepts generated by students rather than by instructors, 2) an activity component where students actively participate in performing tasks (experiments) to test their ideas, 3) an emphasis on learning the methods of verifying and testing hypotheses, and 4) an emphasis on the importance of both content and process as components of learning Some individual studies of the effectiveness of an inquirybased approach have been reported. For example, DiPasquale et al. (2) modified the curriculum in an exercise physiology course at San Diego State University. The course was previously taught in a traditional style. Their new approach was to cover core exercise physiology topics in the first third of the course using the traditional teacher-centered style of learning while emphasizing the scientific process. In the last 9 wk of the course, students worked in small groups of three to four and completed independent research projects. In contrast, Myers and Burgess (11) redesigned an organismal physiology course centering on student-designed experiments throughout the course of the semester. Both studies reported an increase in student achievement of learning outcomes using student-designed experiments compared with a teacher-centered approach. Moreover, a recent review (10) published in Advances of Physiology Education summarized the evidence supporting the conclusion that forms of active learning, such as an inquirybased approach, are more effective in enhancing student learning than traditional modes of teaching. Problems With the Existing Curriculum The physiology curriculum using a teacher-centered approach resulted in several problems related to student learning. One of the problems was that students in our nonmajor course failed to connect physiological concepts taught in lecture with the laboratory activities. In addition, the laboratories did not emphasize the scientific approach to problem solving, and students were restricted in the types of experiments they were able to perform (13). Our old curriculum provided students with detailed step-bystep instructions for completing their experiments. As a result, students commented to the laboratory instructors that they lost sight of the educational purpose of the experiments. Furthermore, regimented instructions did not allow our students any flexibility to deviate from the experimental protocol, thereby impeding student creativity Students had no opportunity to develop their own understanding of physiology using the scientific approach. Even though our majors were required to write laboratory reports in prerequisite courses such as Cell Physiology and Organic Chemistry, they did not communicate their ideas effectively in a scientific report. For example, students did not refer to the neural control of respiration when discussing irregular respiratory patterns when solving a math problem. This resulted in low scores on laboratory reports. Clearly, this called for the need to offer students more opportunities using the scientific method, from researching background information to developing a testable hypothesis using appropriate written communication and reporting of scientific findings. Similar problems in understanding the scientific approach were also evident in our nonmajor course (see Precurricula Survey). Verbal comments from students in our physiology courses indicated a dissatisfaction with simply repeating experiments that had already been done by other researchers. Students could not see the purpose of performing some of the experiments, especially those involving animals, and often asked "Why ar

PM2.5 chemical composition and health risks by inhalation near a chemical complex

Particulate matter (PM2.5) samples were collected in the vicinity of an industrial chemical pole and analysed for organic and elemental carbon (OC and EC), 47 trace elements and around 150 organic constituents. On average, OC and EC accounted for 25.2% and 11.4% of the PM2.5 mass, respectively. Organic compounds comprised polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs, anhydrosugars, phenolics, aromatic ketones, glycerol derivatives, aliphatic alcohols, sterols, and carboxyl groups, including aromatic, carboxylic and dicarboxylic acids. Enrichment factors > 100 were obtained for Pb, Cd, Zn, Cu, Sn, B, Se, Bi, Sb and Mo, showing the contribution of industrial emissions and nearby major roads. Principal component analysis revealed that vehicle, industrial and biomass burning emissions accounted for 66%, 11% and 9%, respectively, of the total PM2.5-bound PAHs. Some of the detected organic constituents are likely associated with plasticiser ingredients and thermal stabilisers used in the manufacture of PVC and other plastics in the industrial complex. Photooxidation products of both anthropogenic (e.g., toluene) and biogenic (e.g., isoprene and pinenes) precursors were also observed. It was estimated that biomass burning accounted for 13.8% of the PM2.5 concentrations and that secondary OC represented 37.6% of the total OC. The lifetime cancer risk from inhalation exposure to PM2.5-bound PAHs was found to be negligible, but it exceeded the threshold of 10?6 for metal(loi)s, mainly due to Cr and As.3518-5DB7-75B0 | M?rio Tom?N/

A new cell primo-culture method for freshwater benthic diatom communities

A new cell primo-culture method was developed for the benthic diatom community isolated from biofilm sampled in rivers. The approach comprised three steps: (1) scraping biofilm from river pebbles, (2) diatom isolation from biofilm, and (3) diatom community culture. With a view to designing a method able to stimulate the growth of diatoms, to limit the development of other microorganisms, and to maintain in culture a community similar to the original natural one, different factors were tested in step 3: cell culture medium (Chu No 10 vs Freshwater “WC” medium modified), cell culture vessel, and time of culture. The results showed that using Chu No 10 medium in an Erlenmeyer flask for cell culture was the optimal method, producing enough biomass for ecotoxicological tests as well as minimising development of other microorganisms. After 96 h of culture, communities differed from the original communities sampled in the two rivers studied. Species tolerant of eutrophic or saprobic conditions were favoured during culture. This method of diatom community culture affords the opportunity to assess, in vitro, the effects of different chemicals or effluents (water samples andindustrial effluents) on diatom communities, as well as on diatom cells, from a wide range of perspectives

European marine omics biodiversity observation network: a strategic outline for the implementation of omics approaches in ocean observation

Marine ecosystems, ranging from coastal seas and wetlands to the open ocean, accommodate a wealth of biological diversity from small microorganisms to large mammals. This biodiversity and its associated ecosystem function occurs across complex spatial and temporal scales and is not yet fully understood. Given the wide range of external pressures on the marine environment, this knowledge is crucial for enabling effective conservation measures and defining the limits of sustainable use. The development and application of omics-based approaches to biodiversity research has helped overcome hurdles, such as allowing the previously hidden community of microbial life to be identified, thereby enabling a holistic view of an entire ecosystem’s biodiversity and functioning. The potential of omics-based approaches for marine ecosystems observation is enormous and their added value to ecosystem monitoring, management, and conservation is widely acknowledged. Despite these encouraging prospects, most omics-based studies are short-termed and typically cover only small spatial scales which therefore fail to include the full spatio-temporal complexity and dynamics of the system. To date, few attempts have been made to establish standardised, coordinated, broad scaled, and long-term omics observation networks. Here we outline the creation of an omics-based marine observation network at the European scale, the European Marine Omics Biodiversity Observation Network (EMO BON). We illustrate how linking multiple existing individual observation efforts increases the observational power in large-scale assessments of status and change in biodiversity in the oceans. Such large-scale observation efforts have the added value of cross-border cooperation, are characterised by shared costs through economies of scale, and produce structured, comparable data. The key components required to compile reference environmental datasets and how these should be linked are major challenges that we address.</jats:p

Factors associated with paradoxical immune response to antiretroviral therapy in HIV infected patients: a case control study

<p>Abstract</p> <p>Background</p> <p>A paradoxical immunologic response (PIR) to Highly Active Antiretroviral Therapy (HAART), defined as viral suppression without CD4 cell-count improvement, has been reported in the literature as 8 to 42%, around 15% in most instances. The present study aims to determine, in a cohort of HIV infected patients in Brazil, what factors were independently associated with such a discordant response to HAART.</p> <p>Methods</p> <p>A case-control study (1:4) matched by gender was conducted among 934 HIV infected patients on HAART in Brazil. Cases: patients with PIR, defined as CD4 < 350 cells/mm³(hazard ratio for AIDS or death of at least 8.5) and undetectable HIV viral load on HAART for at least one year. Controls: similar to cases, but with CD4 counts ≥ 350 cells/mm³. Eligibility criteria were applied. Data were collected from medical records using a standardized form. Variables were introduced in a hierarchical logistic regression model if a p-value < 0.1 was determined in a bivariate analysis.</p> <p>Results</p> <p>Among 934 patients, 39 cases and 160 controls were consecutively selected. Factors associated with PIR in the logistic regression model were: total time in use of HAART (OR 0.981; CI 95%: 0.96-0.99), nadir CD4-count (OR 0.985; CI 95%: 0.97-0.99), and time of undetectable HIV viral load (OR 0.969; CI 95%: 0.94-0.99).</p> <p>Conclusions</p> <p>PIR seems to be related to a delay in the management of immunodeficient patients, as shown by its negative association with nadir CD4-count. Strategies should be implemented to avoid such a delay and improve the adherence to HAART as a way to implement concordant responses.</p