Biology of childhood germ cell tumours, focussing on the significance of microRNAs.

Genomic and protein-coding transcriptomic data have suggested that germ cell tumours (GCTs) of childhood are biologically distinct from those of adulthood. Global messenger RNA profiles segregate malignant GCTs primarily by histology, but then also by age, with numerous transcripts showing age-related differential expression. Such differences are likely to account for the heterogeneous clinico-pathological behaviour of paediatric and adult malignant GCTs. In contrast, as global microRNA signatures of human tumours reflect their developmental lineage, we hypothesized that microRNA profiles would identify common biological abnormalities in all malignant GCTs owing to their presumed shared origin from primordial germ cells. MicroRNAs are short, non-protein-coding RNAs that regulate gene expression via translational repression and/or mRNA degradation. We showed that all malignant GCTs over-express the miR-371-373 and miR-302/367 clusters, regardless of patient age, histological subtype or anatomical tumour site. Furthermore, bioinformatic approaches and subsequent Gene Ontology analysis revealed that these two over-expressed microRNAs clusters co-ordinately down-regulated genes involved in biologically significant pathways in malignant GCTs. The translational potential of this finding has been demonstrated with the detection of elevated serum levels of miR-371-373 and miR-302/367 microRNAs at the time of malignant GCT diagnosis, with levels falling after treatment. The tumour-suppressor let-7 microRNA family has also been shown to be universally down-regulated in malignant GCTs, because of abundant expression of the regulatory gene LIN28. Low let-7 levels resulted in up-regulation of oncogenes including MYCN, AURKB and LIN28 itself, the latter through a direct feedback mechanism. Targeting LIN28, or restoring let-7 levels, both led to effective inhibition of this pathway. In summary, paediatric malignant GCTs show biological differences from their adult counterparts at a genomic and protein-coding transcriptome level, whereas they both display very similar microRNA expression profiles. These similarities and differences may be exploited for diagnostic and/or therapeutic purposes.This is the final version. It was first published by Wiley in Andrology at http://onlinelibrary.wiley.com/doi/10.1111/andr.277/full

Characteristics and prevalence of hardcore smokers attending UK general practitioners

BACKGROUND: Smoking remains a public health problem and although unsolicited GPs' advice against smoking causes between one and three percent of smokers to stop, a significant proportion of smokers are particularly resistant to the notion of stopping smoking. These resistant smokers have been called "hardcore smokers" and although 16% of smokers in the community are hardcore, little is known about hardcore smokers presenting to primary care physicians. Consequently, this study reports the characteristics and prevalence of hardcore smokers attending UK GPs. METHODS: A cross-sectional survey using data from two different research projects was conducted. Data for this analysis had been collected from surgery consultation sessions with 73 GPs in Leicestershire, England, (42 GPs from one project). Research assistants distributed pre-consultation questionnaires to 4147 adults attending GPs' surgery sessions. Questionnaires identified regular smokers, the proportion of hardcore smokers and their characteristics. Non-hardcore and hardcore smokers' ages, gender and nicotine addiction levels were compared. RESULTS: 1170 regular smokers attended surgery sessions and, 16.1% (95% CI, 14.1 to 18.4) were hardcore smokers. Hardcore smokers had higher levels of nicotine addiction than others (p = 0.000), measured by the Heaviness of Smoking Index and were more likely to be male [50.5% hardcore versus 35.3% non-hardcore, (OR = 1.88, 95% CI = 1.4 to 2.6)] but no age differences were observed between groups. CONCLUSION: A significant minority of the smokers who present in general practice are resistant to the notion of smoking cessation and these smokers are more heavily nicotine addicted than others. Although clinical guidelines suggest that GPs should regularly advise all smokers against smoking, it is probable that hardcore smokers do not respond positively to this and help to make up the 97%–99% of smokers who do not quit after being advised to stop smoking by GPs. General practitioners need to find approaches for raising the issue of smoking during consultations in ways that do not reinforce the negative opinions of hardcore smokers concerning smoking cessation

Systematic study of bimodal suspensions of latex nanoparticles using dynamic light scattering

Determining the size of nanoparticles accurately, quickly and easily is becoming more and more important as the use of such particles increases. One of the common techniques for measuring the size of particles in suspension is dynamic light scattering (DLS). In principle, DLS is able to estimate the hydrodynamic particle diameter and its intensity-weighted distribution. However, the measured correlation function or power spectrum must be inverted to obtain this size distribution. The inversion is an ill-posed mathematical problem, and only under certain assumptions can the distribution be determined reliably. Suspensions containing bimodal (or multi-modal) particle size distributions are particularly challenging. This study reports on DLS measurements on a range of bimodal distributions of latex spheres with varying ratios of particle sizes. To determine the efficacy of different inversion techniques, the data has been analyzed both with the algorithms implemented in the DLS instrument's proprietary analysis software and with other inversion routines based on simple analytical models of the particle size distribution. In addition, the results of the DLS analysis have been compared to scanning and transmission electron microscopy (SEM and TEM) measurements. © 2011 The Society of Powder Technology Japan

Star-forming galaxies at very high redshifts

Analysis of the deepest available images of the sky, obtained by the Hubble Space Telescope, reveals a large number of candidate high-redshift galaxies. A catalogue of 1,683 objects is presented, with estimated redshifts ranging from $z=0$ to $z>6$. The high-redshift objects are interpreted as regions of star formation associated with the progenitors of present-day normal galaxies at epochs reaching to 95\% of the time to the Big Bang.Comment: 10 pages, LaTeX type, aaspp4.sty macro provided. Supplementary information, including the full catalog, plots of spectra and redshift likelihood functions for all the objects, and composite spectra, are available at ftp://ftp.ess.sunysb.edu/pub/hd