Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia.

A hallmark of acute myeloid leukemia (AML) is the inability of self-renewing malignant cells to mature into a non-dividing terminally differentiated state. This differentiation block has been linked to dysregulation of multiple cellular processes, including transcriptional, chromatin, and metabolic regulation. The transcription factor HOXA9 and the histone demethylase LSD1 are examples of such regulators that promote differentiation blockade in AML. To identify metabolic targets that interact with LSD1 inhibition to promote myeloid maturation, we screened a small molecule library to identify druggable substrates. We found that differentiation caused by LSD1 inhibition is enhanced by combined perturbation of purine nucleotide salvage and de novo lipogenesis pathways, and identified multiple lines of evidence to support the specificity of these pathways and suggest a potential basis of how perturbation of these pathways may interact synergistically to promote myeloid differentiation. In sum, these findings suggest potential drug combination strategies in the treatment of AML.

Co-expression of the neuropeptide proctolin and glutamate in the central nervous system, along mechanosensory neurons and leg muscle in Cupiennius salei.

Similar to hair cells in the mammalian cochlear system, mechanosensory neurons in the Central American wandering spider Cupiennius salei are strongly innervated by efferent fibers that originate from neurons whose somata are located in the central nervous system (CNS). In both the mammalian and arachnid systems, efferent fibers have been shown to co-express two or more transmitters; however, our understanding regarding co-transmission and how it affects sensory signal transduction and processing in these systems is only fragmentary. The spider model system is exceptionally suitable for this type of investigation due to the large size and easy accessibility of the sensory and efferent neurons in this system. Thus far, GABA and glutamate have been identified as the main fast-acting transmitters in efferent axons that form synaptic contacts onto sensory neurons in slit sense organs. Ultrastructural investigations suggest an abundance of neuropeptides within these peripheral synapses. In an effort to identify these peptides and conduct functional studies, we have employed immunohistochemistry to investigate whether the neuropeptide proctolin is present in neurons of the leg ganglia and in peripheral leg structures. Here, we demonstrate that ~ 73% of all neurons in the CNS of C. salei show proctolin-like immunoreactivity (proc-LIR) including the leg ganglia. We demonstrate that both strongly and weakly labeled neurons can be distinguished. The majority of proc-LIR neurons show weak labeling intensity and ~ 86.2% co-localize with glutamate. In future experiments, we plan to undertake functional studies to investigate the significance of this co-expression, which has yet to be investigated.

We love our school toilets: involving primary school students in improving their school toilets.

This article reports on the planning, implementation and evaluation of an intervention to improve school students' experience of using the school toilet in a primary school in Melbourne, Australia. 20 students from grades 2-6 participated in focus groups, to discuss what they valued about the school and raise awareness of issues they were not happy about. A common theme from all of the focus groups was that students reported avoiding use of the school toilets. Using the ideas generated from the focus groups, the student council (with input from staff), developed a self-administered pre- and post-test questionnaire. This was given to 220 students in grades 1-4, aged 6-10 years. Improvements suggested by the students were made to the toilet block, and then a post-test was administered. Independent t tests were conducted. The pre-test indicated that 71% of girls and 65% of boys feared the behaviour of other students in the toilet. Overwhelmingly, the qualitative comments focused on poor student behaviour in the toilets, with lack of privacy due to student misbehaviour mentioned in 90% of the comments. After the toilets were revamped, the greatest gains were made in students' attitudes toward the toilets, with a 37% increase in students who indicated they now liked the toilet facility. Incidents of vandalism also decreased; however, student misconduct in the toilets was still regarded as a problem. Involving students in refurbishing their toilets improved how students viewed the toilets and reduced vandalism; however, a different intervention is required to change inappropriate behaviours in the toilet.

Becoming a health promoting school: key components of planning.

This article looks at the practicalities of implementing the health promoting school (HPS) framework, including conducting a whole school audit, to enable a primary school to successfully adopt the HPS principles. A partnership agreement was signed, between EACH Social and Community Health which is a local Community Health Centre and a primary school in the Eastern suburbs of Melbourne, in Australia. An audit was conducted of the school community with four follow up focus groups of students from grades 3 to 6. Qualitative data was gathered from 20 teachers at the school at a professional development day facilitated by the health promotion staff of the Community Health Centre. The results of the school audit identified that students in grades 3 to 6 and parents valued the outside environment of the school most highly. The staff valued staff attributes most highly. Suggestions from students to improve the school included improving the canteen and outside environment. Staff were most concerned about fitness of both the staff and the students. Parents also identified lack of healthy eating as a concern. The school community sees the value of adopting the HPS framework, however on-going structured support is required if the school is to successfully adopt the HPS approach. The school community needs to understand that the move toward cultural and environmental change is slow. Successful adoption of the HPS model requires time and collaboration. The emphasis needs to be on supporting teachers to change their school from within. Relationships are important.