Discrimination of prostate cancer cells and non-malignant cells using secondary ion mass spectrometry

This communication utilises Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) combined with multivariate analysis to obtain spectra from the surfaces of three closely related cell lines allowing their discrimination based upon mass spectral ions

Seismic wave propagation around subsurface igneous sill complexes

Acknowledgements This work was undertaken during O.G.S’s PhD at Durham University, funded by Eni through the Volcanic Margins Research Consortium (Phase 2). Seismic modelling was performed using the open source SOFI2D (Bohlen 2002) and post-processed using Seismic Un*x (Stockwell & Cohen 2012). Figures were prepared using the open source Generic Mapping Tools (GMT) (Wessel & Smith W. H. F. 1998) and Seismic Un*x. Zoeppritz amplitude coefficients were calculated using the CREWES Matlab toolbox of the University of Calgary (Margrave and Lamoureux 2019). This work made use of the facilities of the Hamilton HPC Service of Durham UniversityPeer reviewe

Measurements of the Diffuse Ultraviolet Background and the Terrestrial Airglow with the Space Telescope Imaging Spectrograph

Far-UV observations in and near the Hubble Deep Fields demonstrate that the Space Telescope Imaging Spectrograph (STIS) can potentially obtain unique and precise measurements of the diffuse far-ultraviolet background. Although STIS is not the ideal instrument for such measurements, high-resolution images allow Galactic and extragalactic objects to be masked to very faint magnitudes, thus ensuring a measurement of the truly diffuse UV signal. The programs we have analyzed were not designed for this scientific purpose, but would be sufficient to obtain a very sensitive measurement if it were not for a weak but larger-than-expected signal from airglow in the STIS 1450-1900 A bandpass. Our analysis shows that STIS far-UV crystal quartz observations taken near the limb during orbital day can detect a faint airglow signal, most likely from NI\1493, that is comparable to the dark rate and inseparable from the far-UV background. Discarding all but the night data from these datasets gives a diffuse far-ultraviolet background measurement of 501 +/- 103 ph/cm2/sec/ster/A, along a line of sight with very low Galactic neutral hydrogen column (N_HI = 1.5E20 cm-2) and extinction (E(B-V)=0.01 mag). This result is in good agreement with earlier measurements of the far-UV background, and should not include any significant contribution from airglow. We present our findings as a warning to other groups who may use the STIS far-UV camera to observe faint extended targets, and to demonstrate how this measurement may be properly obtained with STIS.Comment: 7 pages, Latex. 4 figures. Uses corrected version of emulateapj.sty and apjfonts.sty (included). Accepted for publication in A

NMR resonance assignments of RNase P protein from \u3cem\u3eThermotoga maritima\u3c/em\u3e

Ribonuclase P (RNase P) is an essential metallo-endonuclease that catalyzes 5′ precursor-tRNA (ptRNA) processing and exists as an RNA-based enzyme in bacteria, archaea, and eukaryotes. In bacteria, a large catalytic RNA and a small protein component assemble to recognize and accurately cleave ptRNA and tRNA-like molecular scaffolds. Substrate recognition of ptRNA by bacterial RNase P requires RNA-RNA shape complementarity, intermolecular base pairing, and a dynamic protein-ptRNA binding interface. To gain insight into the binding specificity and dynamics of the bacterial protein-ptRNA interface, we report the backbone and side chain 1H, 13C, and 15N resonance assignments of the hyperthermophilic Thermatoga maritima RNase P protein in solution at 318 K. Our data confirm the formation of a stable RNA recognition motif (RRM) with intrinsic heterogeneity at both the N- and C-terminus of the protein, consistent with available structural information. Comprehensive resonance assignments of the bacterial RNase P protein serve as an important first step in understanding how coupled RNA binding and protein-RNA conformational changes give rise to ribonucleoprotein function

Do walking strategies to increase physical activity reduce reported sitting in workplaces: a randomized control trial

Background Interventions designed to increase workplace physical activity may not automatically reduce high volumes of sitting, a behaviour independently linked to chronic diseases such as obesity and type II diabetes. This study compared the impact two different walking strategies had on step counts and reported sitting times. Methods Participants were white-collar university employees (n = 179; age 41.3 ± 10.1 years; 141 women), who volunteered and undertook a standardised ten-week intervention at three sites. Pre-intervention step counts (Yamax SW-200) and self-reported sitting times were measured over five consecutive workdays. Using pre-intervention step counts, employees at each site were randomly allocated to a control group (n = 60; maintain normal behaviour), a route-based walking group (n = 60; at least 10 minutes sustained walking each workday) or an incidental walking group (n = 59; walking in workday tasks). Workday step counts and reported sitting times were re-assessed at the beginning, mid- and endpoint of intervention and group mean± SD steps/day and reported sitting times for pre-intervention and intervention measurement points compared using a mixed factorial ANOVA; paired sample-t-tests were used for follow-up, simple effect analyses. Results A significant interactive effect (F = 3.5; p < 0.003) was found between group and step counts. Daily steps for controls decreased over the intervention period (-391 steps/day) and increased for route (968 steps/day; t = 3.9, p < 0.000) and incidental (699 steps/day; t = 2.5, p < 0.014) groups. There were no significant changes for reported sitting times, but average values did decrease relative to the control (routes group = 7 minutes/day; incidental group = 15 minutes/day). Reductions were most evident for the incidental group in the first week of intervention, where reported sitting decreased by an average of 21 minutes/day (t = 1.9; p < 0.057). Conclusion Compared to controls, both route and incidental walking increased physical activity in white-collar employees. Our data suggests that workplace walking, particularly through incidental movement, also has the potential to decrease employee sitting times, but there is a need for on-going research using concurrent and objective measures of sitting, standing and walking

Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis

BackgroundAtopic dermatitis (AD; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear.ObjectiveWe sought to interrogate tissue-specific variations in the expressed genome in the skin of children with AD and to investigate underlying pathomechanisms in atopic skin.MethodsWe applied single-molecule direct RNA sequencing to analyze the whole transcriptome using minimal tissue samples. Uninvolved skin biopsy specimens from 26 pediatric patients with AD were compared with site-matched samples from 10 nonatopic teenage control subjects. Cases and control subjects were screened for FLG genotype to stratify the data set.ResultsTwo thousand four hundred thirty differentially expressed genes (false discovery rate, P < .05) were identified, of which 211 were significantly upregulated and 490 downregulated by greater than 2-fold. Gene ontology terms for “extracellular space” and “defense response” were enriched, whereas “lipid metabolic processes” were downregulated. The subset of FLG wild-type cases showed dysregulation of genes involved with lipid metabolism, whereas filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon–mediated stress response.ConclusionThese analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology independent of FLG genotype, whereas an aberrant defense response is seen in subjects with FLG mutations. Genotype stratification of the large data set has facilitated functional interpretation and might guide future therapy development

Towards understanding interactions between Sustainable Development Goals: the role of environment–human linkages

Only 10 years remain to achieve all Sustainable Development Goals (SDGs) globally, so there is a growing need to increase the effectiveness and efficiency of action by targeting multiple SDGs. The SDGs were conceived as an ‘indivisible whole’, but interactions between SDGs need to be better understood. Several previous assessments have begun to explore interactions including synergies and possible conflicts between the SDGs, and differ widely in their conclusions. Although some highlight the role of the more environmentally-focused SDGs in underpinning sustainable development, none specifically focuses on environment-human linkages. Assessing interactions between SDGs, and the influence of environment on them, can make an important contribution to informing decisions in 2020 and beyond. Here, we review previous assessments of interactions among SDGs, apply an influence matrix to assess pairwise interactions between all SDGs, and show how viewing these from the perspective of environment-human linkages can influence the outcome. Environment, and environment-human linkages, influence most interactions between SDGs. Our action-focused assessment enables decision makers to focus environmental management to have the greatest impacts, and to identify opportunities to build on synergies and reduce trade-offs between particular SDGs. It may enable sectoral decision makers to seek support from environment managers for achieving their goals. We explore cross-cutting issues and the relevance and potential application of our approach in supporting decision making for progress to achieve the SDGs

Kinetochore assembly and heterochromatin formation occur autonomously in Schizosaccharomyces pombe

Kinetochores in multicellular eukaryotes are usually associated with heterochromatin. Whether this heterochromatin simply promotes the cohesion necessary for accurate chromosome segregation at cell division or whether it also has a role in kinetochore assembly is unclear. Schizosaccharomyces pombe is an important experimental system for investigating centromere function, but all of the previous work with this species has exploited a single strain or its derivatives. The laboratory strain and most other S. pombe strains contain three chromosomes, but one recently discovered strain, CBS 2777, contains four. We show that the genome of CBS 2777 is related to that of the laboratory strain by a complex chromosome rearrangement. As a result, two of the kinetochores in CBS 2777 contain the central core sequences present in the laboratory strain centromeres, but lack adjacent heterochromatin. The closest block of heterochromatin to these rearranged kinetochores is ∼100 kb away at new telomeres. Despite lacking large amounts of adjacent heterochromatin, the rearranged kinetochores bind CENP-ACnp1 and CENP-CCnp3 in similar quantities and with similar specificities as those of the laboratory strain. The simplest interpretation of this result is that constitutive kinetochore assembly and heterochromatin formation occur autonomously