Reciprocal t(9;22) ABL/BCR fusion proteins: leukemogenic potential and effects on B cell commitment

Background: t(9;22) is a balanced translocation, and the chromosome 22 breakpoints (Philadelphia chromosome – Ph+) determine formation of different fusion genes that are associated with either Ph+ acute lymphatic leukemia (Ph+ ALL) or chronic myeloid leukemia (CML). The "minor" breakpoint in Ph+ ALL encodes p185BCR/ABL from der22 and p96ABL/BCR from der9. The "major" breakpoint in CML encodes p210BCR/ABL and p40ABL/BCR. Herein, we investigated the leukemogenic potential of the der9-associated p96ABL/BCR and p40ABL/BCR fusion proteins and their roles in the lineage commitment of hematopoietic stem cells in comparison to BCR/ABL. Methodology: All t(9;22) derived proteins were retrovirally expressed in murine hematopoietic stem cells (SL cells) and human umbilical cord blood cells (UCBC). Stem cell potential was determined by replating efficiency, colony forming - spleen and competitive repopulating assays. The leukemic potential of the ABL/BCR fusion proteins was assessed by in a transduction/transplantation model. Effects on the lineage commitment and differentiation were investigated by culturing the cells under conditions driving either myeloid or lymphoid commitment. Expression of key factors of the B-cell differentiation and components of the preB-cell receptor were determined by qRT-PCR. Principal Findings: Both p96ABL/BCR and p40ABL/BCR increased proliferation of early progenitors and the short term stem cell capacity of SL-cells and exhibited own leukemogenic potential. Interestingly, BCR/ABL gave origin exclusively to a myeloid phenotype independently from the culture conditions whereas p96ABL/BCR and to a minor extent p40ABL/BCR forced the B-cell commitment of SL-cells and UCBC. Conclusions/Significance: Our here presented data establish the reciprocal ABL/BCR fusion proteins as second oncogenes encoded by the t(9;22) in addition to BCR/ABL and suggest that ABL/BCR contribute to the determination of the leukemic phenotype through their influence on the lineage commitment

Developing an assessed reading portfolio to improve reading habits and raise test results

For over 10 years, preparatory students at Khalifa University, UAE, have been encouraged to improve their reading and language learning skills through the use of an assessed reading portfolio. This paper briefly outlines the rationale behind this type of assessment and the design features of the portfolio, before detailing some of the many adaptations that it has experienced over the years, paying particular attention to recent developments involving the use of technology. Through an evaluation of the portfolio, using authentic scores for the portfolio and comparing them to IELTS reading test scores, it emerges that students who do well on the portfolio are more likely to make gains in their reading scores than those who do not perform well in their reading portfolio assessment

Practices of conformity and transgression in an out-of-school reading programme for 'at risk' children

A large body of research has demonstrated that the plurilingualisms and pluriliteracies that children and youth bring to classrooms are often not those required for school success. This is even more so for students from underprivileged backgrounds, a demographic where children and youth with family backgrounds of immigration are over-represented. This article reports on ethnographic research at an after-school reading programme for primary school children considered to be at risk of school failure in the old town of Barcelona. Results suggest that the practices of pluriliteracy supported by the programme often conform with those inherent to the children's formal education; that is, with the very practices that have contributed to the children being placed in the programme to begin with. However, through the fine-grained analysis of child-volunteer interactions, certain practices that subtly transgress these norms are identified. It is in such practices that we see potential for educational transformation

Probing metal ion binding and conformational properties of the colicin E9 endonuclease by electrospray ionization time-of-flight mass spectrometry

Nano-electrospray ionization time-of-flight mass spectrometry (ESI-MS) was used to study the conformational consequences of metal ion binding to the colicin E9 endonuclease (E9 DNase) by taking advantage of the unique capability of ESI-MS to allow simultaneous assessment of conformational heterogeneity and metal ion binding. Alterations of charge state distributions on metal ion binding/release were correlated with spectral changes observed in far- and near-UV circular dichroism (CD) and intrinsic tryptophan fluorescence. In addition, hydrogen/deuterium (H/D) exchange experiments were used to probe structural integrity. The present study shows that ESI-MS is sensitive to changes of the thermodynamic stability of E9 DNase as a result of metal ion binding/release in a manner consistent with that deduced from proteolysis and calorimetric experiments. Interestingly, acid-induced release of the metal ion from the E9 DNase causes dramatic conformational instability associated with a loss of fixed tertiary structure, but secondary structure is retained. Furthermore, ESI-MS enabled the direct observation of the noncovalent protein complex of E9 DNase bound to its cognate immunity protein Im9 in the presence and absence of Zn2+. Gas-phase dissociation experiments of the deuterium-labeled binary and ternary complexes revealed that metal ion binding, not Im9, results in a dramatic exchange protection of E9 DNase in the complex. In addition, our metal ion binding studies and gas-phase dissociation experiments of the ternary E9 DNase-Zn2+-Im9 complex have provided further evidence that electrostatic interactions govern the gas phase ion stability

Research ethics

Qualitative research, especially studies in educational contexts, often brings up questions of ethics because the study design involves human subjects, some of whom are under age (eg data collected in primary education classrooms). It is not always easy for young researchers to anticipate where ethical issues might emerge while designing their research project. So what are some questions that a researcher might consider? A first premise for a researcher is to 'do no harm'. It is important for the researcher to try to think about any adverse effects the study could possibly have on any of the participants. Of course, even though the researcher may try to anticipate any potential ethical issues, unexpected adverse effects may occur, in which case, the study should be halted or modified

Is English important in your life? : A collaborative experience in a secondary school

In this chapter, we describe a collaborative action-research project involving an ethnographer, an English teacher and secondary school students in the production of videos about the role of English in the youths' lives. Building on the principles of language socialisation and imagined communities, the analysis of the videos produced by the students foregrounds the connections between their socialisation into English, their sense of present and future investment in English learning activities and their engagement with imagined communities of YouTubers and Instagrammers. Social media, digital platforms and private after- school language colleges emerge as central in young people's English language learning trajectories, alongside their formal education. We conclude that collaborative action- research initiatives might provide teachers, researchers and students with opportunities to connect youths' in- and out- of- school practices and engage them in more meaningful English learning experiences

Effect of Process Parameters on Bioelectricity Production, Energy and Environmental Performance

This study evaluates the energy and environmental performance of a cogeneration system operating simultaneously with bagasse and straw in a rankine cycle. Different process conditions, defined in terms of boiler operating pressure, moisture content and straw addition rate, were analyzed. The combination of these parameters led to the elaboration of one hundred and twenty-five analysis scenarios. The energy profile was based on the energy performance indicator, which is the ratio between the exported electricity and the intrinsic energy of biomass consumed for its generation, and the environmental assessment was performed in terms of climate change. Scenario modeling was developed according to the conceptual framework proposed by the life cycle assessment technique with a ‘from cradle-to-gate’ coverage. Results indicate that the best energy and environmental performances (energy performance indicator = 0.193 and 688 kg CO2eq/MWh) were obtained with the highest pressure (100 bar) and addition rate (50%), and the lowest moisture content (10%). Moreover, straw moisture has more influence on the system environmental performance than its addition rate

Out-of-school language learning and educational equity

This chapter explores existing scholarship on out-of-school learning at both a local (Catalan) and an international level. We particularly focus on research that documents foreign language learning and literacy development in both informal and nonformal education across diverse socioeconomic, linguistic and cultural contexts. Research shows that access to extracurricular initiatives and opportunities to engage in informal language learning can positively impact upon formal academic achievement and future professional trajectories, especially for economically under- resourced students, and thus can play a significant role in tackling socioeducational inequalities. These positive effects are enhanced when out-of-school initiatives focus on students' competences and build on their linguistic and cultural funds of knowledge to include their everyday communicative practices. However, while offer of and demand for out- of- school learning - and particularly of foreign language learning - have increased in recent years, so too have inequalities in participation between more and less affluent families, in part due to economic burdens such as access fees, and to public restraints on funding and scholarships

Exploring how family carers of a person with dementia manage pre-death grief: A mixed methods study

Objectives: Many family carers of a person with dementia experience pre-death grief. We aimed to identify strategies that help carers manage pre-death grief. We hypothesised that emotion and problem focussed styles would be associated with lower, and dysfunctional coping with higher grief intensity. Methods: Mixed methods observational study using structured and semi-structured interviews with 150 family carers of people with dementia living at home or in a care home. Most participants were female (77%), caring for a parent (48%) or partner/spouse (47%) with mild (25%), moderate (43%) or severe (32%) dementia. They completed the Marwit-Meuser Caregiver Grief Inventory Short Form and the Brief Coping Orientation to Problems Experienced (Brief-COPE) questionnaire. We asked carers to identify strategies used for managing grief. We recorded field notes for 150 interviews and audio-recorded additional interviews with a sub-sample of 16 participants. Results: Correlations indicated that emotion-oriented coping was associated with lower grief (R = −0.341), and dysfunctional coping with higher grief (R = 0.435), with a small association with problem-focused strategies (R = −0.109), partly supporting our hypothesis. Our qualitative themes broadly match the three Brief-COPE styles. Unhelpful strategies of denial and avoidance align with dysfunctional coping strategies. Psychological strategies (including acceptance and humour) and seeking support were consistent with emotion-focused strategies, but we did not identify a theme relating to problem-focused strategies. Conclusion: Most carers identified multiple strategies for processing grief. Carers could readily identify supports and services that they found helpful for managing pre-death grief, yet current services appear under-resourced to meet growing demand. (ClinicalTrials.gov ID: NCT03332979)