Disproportionate Expression of ATM in Cerebellar Cortex During Human Neurodevelopment.

Cerebellar neurodegeneration is a classical feature of ataxia telangiectasia (A-T), an autosomal recessive condition caused by loss-of-function mutation of the ATM gene, a gene with multiple regulatory functions. The increased vulnerability of cerebellar neurones to degeneration compared to cerebral neuronal populations in individuals with ataxia telangiectasia implies a specific importance of intact ATM function in the cerebellum. We hypothesised that there would be elevated transcription of ATM in the cerebellar cortex relative to ATM expression in other grey matter regions during neurodevelopment in individuals without A-T. Using ATM transcription data from the BrainSpan Atlas of the Developing Human Brain, we demonstrate a rapid increase in cerebellar ATM expression relative to expression in other brain regions during gestation and remaining elevated during early childhood, a period corresponding to the emergence of cerebellar neurodegeneration in ataxia telangiectasia patients. We then used gene ontology analysis to identify the biological processes represented in the genes correlated with cerebellar ATM expression. This analysis demonstrated that multiple processes are associated with expression of ATM in the cerebellum, including cellular respiration, mitochondrial function, histone methylation, and cell-cycle regulation, alongside its canonical role in DNA double-strand break repair. Thus, the enhanced expression of ATM in the cerebellum during early development may be related to the specific energetic demands of the cerebellum and its role as a regulator of these processes.

The Regulation of m6A Modification in Glioblastoma: Functional Mechanisms and Therapeutic Approaches.

Glioblastoma is the most prevalent primary brain tumour and invariably confers a poor prognosis. The immense intra-tumoral heterogeneity of glioblastoma and its ability to rapidly develop treatment resistance are key barriers to successful therapy. As such, there is an urgent need for the greater understanding of the tumour biology in order to guide the development of novel therapeutics in this field. N6-methyladenosine (m6A) is the most abundant of the RNA modifications in eukaryotes. Studies have demonstrated that the regulation of this RNA modification is altered in glioblastoma and may serve to regulate diverse mechanisms including glioma stem-cell self-renewal, tumorigenesis, invasion and treatment evasion. However, the precise mechanisms by which m6A modifications exert their functional effects are poorly understood. This review summarises the evidence for the disordered regulation of m6A in glioblastoma and discusses the downstream functional effects of m6A modification on RNA fate. The wide-ranging biological consequences of m6A modification raises the hope that novel cancer therapies can be targeted against this mechanism.

Referrers' point of view on the referral process to neurosurgery and opinions on neurosurgeons: a large-scale regional survey in the UK.

OBJECTIVES: There is an increased reliance on online referral systems (ORS) within neurosurgical departments across the UK. Opinions of neurosurgeons on ORS are extensively reported but those of referrers have hardly been sought. Our study aims at ascertaining our referring colleagues' views on our ORS and its impact on patient care, their opinions on neurosurgeons and how to improve our referral process. SETTING: 14 district general hospitals and one teaching hospital. PARTICIPANTS: 641 healthcare professionals across a range of medical and surgical specialties including doctors of all grades, nurses and physiotherapists. Survey responses were obtained by medical students using a smartphone application. RESULTS: Although 92% of respondents were aware of the ORS, 74% would routinely phone the on-call registrar either before or after making referrals online. The majority (44%) believed their call to relate to a life-threatening emergency. 62% of referrers considered the ORS helpful in informing patients' care and 48% had a positive opinion of their interaction with neurosurgical registrars. On ways to improve the ORS, 50% selected email/text confirmation of response sent to referrers and 16% to referring consultants. CONCLUSION: Our results confirm that referrers feel that using our ORS positively impacts patient care but that it remains in need of improvement in order to better suit our colleagues' needs when it comes to managing neurosurgical patients. We feel that the promotion of neurosurgical education and mitigation of the effects of adverse workplace human factors are likely to achieve the common goal of neurosurgeons and referrers alike: a high standard in patient care.