Regulation of the Na,K-ATPase Gamma-Subunit FXYD2 by Runx1 and Ret Signaling in Normal and Injured Non-Peptidergic Nociceptive Sensory Neurons

Dorsal root ganglia (DRGs) contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions. In this study we reveal that FXYD2, which encodes the gamma-subunit of the Na,K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. In non-peptidergic nociceptors, we show that the transcription factor Runx1 controls FXYD2 expression during the maturation of the somato-sensory system, partly through regulation of the tyrosine kinase receptor Ret. Moreover, Ret signaling maintains FXYD2 expression in adults as demonstrated by the axotomy-induced down-regulation of the gene that can be reverted by in vivo delivery of GDNF family ligands. Altogether, these results establish FXYD2 as a specific marker of defined sensory neuron subtypes and a new target of the Ret signaling pathway during normal maturation of the non-peptidergic nociceptive neurons and after sciatic nerve injury

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Perspectives of dentists on smoking cessation in Hong Kong

Objective: To assess the views of dentists in conducting smoking cessation counselling in dental practices in Hong Kong. Methods: A mailed questionnaire survey was conducted on a random sample of 484 Hong Kong dentists. Information on belief, attitudes and confidence of the dentists' roles towards smoking cessation counselling; current practices and perceived barriers in conducting smoking cessation counselling; and personal information of the dentists were collected. Results: 211 dentists completed the questionnaires (response rate: 50.2%). Most of the surveyed dentists had positive attitudes on the necessity of guidelines for dentists in conducting smoking cessation counselling. More than half of the surveyed dentists (55.0%) asked and recorded the patients' smoking status routinely in their practices. The top three barriers perceived by the dentists were: “lack of patients' motivation” (85.6%), “lack of time in consultation” (73.5%) and “lack of smoking cessation protocols and guidelines” (68.1%). Dentists who were females, younger, had fewer years of practice, graduated in Hong Kong or practiced in non-private hospitals/clinics were more likely to ask and record the patients' smoking status (p<0.05). For those surveyed dentists who had a more positive view on belief, attitudes and confidence of the dentists' roles towards smoking cessation counselling, they were more readily to carry out smoking cessation counselling activities (p<0.05). Conclusion: Dentists in Hong Kong had positive belief and attitudes but inadequate confidence towards their roles in smoking cessation counselling. Smoking cessation counselling activities were not actively carried out by dentists in Hong Kong

Perspectives of the dentists on smoking cessation in Hong Kong

Objectives. To describe dentists’ current practices in conducting smoking cessation counseling and to investigate factors associated with an active role in such counseling in Hong Kong. Methods. A mailed questionnaire survey was conducted on a random sample of 484 Hong Kong dentists. Information on beliefs, attitudes, and confidence of the dentists towards smoking cessation counseling, current practices, and perceived barriers to such counseling, as well as personal information about the dentists were collected. Results. A total of 211 dentists completed the questionnaires. More than half of the respondents (55%) asked and recorded patient smoking status routinely in their practices. Among them, over 90% advised smokers to quit and explained the associated health risks to them. Less than half (47%) assessed each patient’s willingness to attempt quitting. Around one third of the dentists provided printed resources to patients about smoking cessation (37%), assisted patients in smoking cessation (38%), and arranged follow-ups (36%). Multiple logistic regression showed that dentists who were female (odds ratio=3.5, P=0.001), graduated in Hong Kong (odds ratio=3.6, P<0.001), and had received training related to smoking cessation (odds ratio=7.3, P<0.001) had a significantly higher chance of asking and recording the patients’ smoking status. The top three barriers perceived by the dentists in conducting smoking cessation counseling were lack of patient motivation, lack of time in the consultation, and lack of smoking cessation protocols and guidelines. Conclusions. Smoking cessation counseling activities were not actively carried out by dentists in Hong Kong. Factors associated with dentists who asked and recorded the patient’s smoking status were gender, place of graduation, and receipt of relevant training. patient’s smoking status were gender, place of graduation, and receipt of relevant training