miR-9 Acts as an OncomiR in Prostate Cancer through Multiple Pathways That Drive Tumour Progression and Metastasis

Identification of dysregulated microRNAs (miRNAs) in prostate cancer is critical not only for diagnosis, but also differentiation between the aggressive and indolent forms of the disease. miR-9 was identified as an oncomiR through both miRNA panel RT-qPCR as well as high-throughput sequencing analysis of the human P69 prostate cell line as compared to its highly tumorigenic and metastatic subline M12, and found to be consistently upregulated in other prostate cell lines including DU-145 and PC3. While miR-9 has been characterized as dysregulated either as an oncomiR or tumour suppressor in a variety of other cancers including breast, ovarian, and nasopharyngeal carcinomas, it has not been previously evaluated and proven as an oncomiR in prostate cancer. miR-9 was confirmed an oncomiR when found to be overexpressed in tumour tissue as compared to adjacent benign glandular epithelium through laser-capture microdissection of radical prostatectomy biopsies. Inhibition of miR-9 resulted in reduced migratory and invasive potential of the M12 cell line, and reduced tumour growth and metastases in male athymic nude mice. Analysis showed that miR-9 targets e-cadherin and suppressor of cytokine signalling 5 (SOCS5), but not NF-ĸB mRNA. Expression of these proteins was shown to be affected by modulation in expression of miR-9

Acute and chronic effects of foam rolling vs eccentric exercise on ROM and force output of the plantar flexors

Foam rolling and eccentric exercise interventions have been demonstrated to improve range of motion (ROM). However, these two modalities have not been directly compared. Twenty-three academy soccer players (age: 18 ± 1; height: 1.74 ± 0.08 m; body mass: 69.3 ± 7.5 kg) were randomly allocated to either a foam rolling (FR) or eccentric exercise intervention designed to improve dorsiflexion ROM. Participants performed the intervention daily for a duration of four weeks. Measurements of dorsiflexion ROM, isometric plantar flexion torque and drop jump reactive strength index were taken at baseline (pre-intervention) and at three subsequent time-points (30-min post, 24-hours post and 4-weeks post). A significant time x group interaction effect was observed for dorsiflexion (P = 0.036), but not for torque or reactive strength index. For dorsiflexion, there was a significant increase in both acute (30-min; P < 0.001) and chronic (4-week; P < 0.001) ROM for the eccentric group, whilst FR exhibited only an acute improvement (P < 0.001). Eccentric training would appear a more efficacious modality than foam rolling for improving dorsiflexion ROM in elite academy soccer players

Producing airspace : the contested geographies of Nottingham East Midlands Airport

During the last 100 years, commercial aviation has developed into an established mode of transportation serving millions of passengers every year, but while researchers from other disciplines - most notably sociology, cultui-al history, and anthropology - have begun to appreciate the multiple dimensions of flight, geographers have written surprisingly little on the subject beyond quantitative analyses of airline networks. While perhaps understandable given the present geopolitical climate of passenger (in)security and commercial confidentiality, this nevertheless means many of the industry's significant facets have yet to be adequately charted. Considering geography's rich heritage of examining space, place, and spatial phenomena at a variety of scales, this thesis provides a distinctive contribution to theoretical and empirical knowledge by addressing the multiple geographies of airspace. Set in the context of the ongoing controversy surrounding the reorganisation offlightpaths at Nottingham East Midlands Airport (NEMA) in the United Kingdom, it considers the inherently geographical and often contested nature of airspace production. By detailing the complex interplay between how airspace is produced 'on the ground' by those who oppose its use, and 'in the air' by Air Traffic Controllers and airline pilots, it offers a new perspective for studies of geography and air transport in an age of mass aeromobility.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Ecological innovations in the Cambrian and the origins of the crown group phyla

One contribution of 16 to a discussion meeting issue &apos;Homology and convergence in nervous system evolution&apos;

Floating stones off El Hierro, Canary Islands: xenoliths of pre-island sedimentary origin in the early products of the October 2011 eruption

The eruption that started off the south coast of El Hierro, Canary Islands, in October 2011 has emitted intriguing eruption products found floating in the sea. These specimens appeared as floating volcanic "bombs" that have in the meantime been termed "restingolites" (after the close-by village of La Restinga) and exhibit cores of white and porous pumice-like material. Currently the nature and origin of these "floating stones" is vigorously debated among researchers, with important implications for the interpretation of the hazard potential of the ongoing eruption. The "restingolites" have been proposed to be either (i) juvenile high-silica magma (e.g. rhyolite), (ii) remelted magmatic material (trachyte), (iii) altered volcanic rock, or (iv) reheated hyaloclastites or zeolite from the submarine slopes of El Hierro. Here, we provide evidence that supports yet a different conclusion. We have collected and analysed the structure and composition of samples and compared the results to previous work on similar rocks found in the archipelago. Based on their high silica content, the lack of igneous trace element signatures, and the presence of remnant quartz crystals, jasper fragments and carbonate relicts, we conclude that "restingolites" are in fact xenoliths from pre-island sedimentary rocks that were picked up and heated by the ascending magma causing them to partially melt and vesiculate. They hence represent messengers from depth that help us to understand the interaction between ascending magma and crustal lithologies in the Canary Islands as well as in similar Atlantic islands that rest on sediment/covered ocean crust (e.g. Cape Verdes, Azores). The occurrence of these "restingolites" does therefore not indicate the presence of an explosive high-silica magma that is involved in the ongoing eruption

Long-term effects of ocean temperature rise on the deep sea

The Comprehensive Nuclear Test Ban Treaty Organization operates a global International Monitoring System, with 11 hydroacoustic stations around the globe located in the deep-sea sound channel. Continuous measurements provide up to 20 years of sound pressures at frequencies of up to 100 Hz, depending on when each station was installed. These relatively long timescales allow investigating the effects of climate over that period. This presentation will show data from CTBT stations H11 (Wake Island, in the North Pacific) and H01 (Cape Leeuwin, in the Indian Ocean). Multiscale aggregations of 1-minute power spectral density (PSD) levels and sound energy measures over several days are used to show their correlation with sea surface temperature (SST) measurements at different timescales. In particular, we can detect seasonal changes in the SST as well as longer term climatic variations. The spectral analysis also shows periodic features in PSD levels around 15 to 31 Hz. The Intergovernmental Panel on Climate Change concluded in 2014 that the increase in temperature has mostly affected the upper (0 - 700 m) ocean while assessing the impact of climate change in the deep sea (> 1000 m) is a challenging task due to the difficulty of gathering long-term comprehensive data. This link between sound pressure levels at 1-km depths and the surface temperature of the ocean is particularly important. Sound is an Essential Ocean Variable, and a key factor to better understand the Earth’s climate system

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

PIM-1 membranes containing POSS - graphene oxide for CO2 separation

PIM-1 mixed matrix membranes (MMMs) were fabricated with polyhedral oligomeric silsesquioxane (POSS) and graphene oxide (GO) functionalized with POSS (GO-POSS), and tested for CO2/N2 (single gas) and CO2/CH4 (1:1, v:v gas mixture). The CO2 permeability of the best performing fresh MMM (containing 0.05 wt% GO-POSS) was ~ 12000 Barrer, which is 69% higher than that of the neat PIM-1 membrane, with about the same selectivity (CO2/CH4 selectivity ~ 12 and CO2/N2 selectivity ~ 20). In both cases, the gas separation data surpass the 2008 Robeson upper bound. In addition to the initial CO2 permeability enhancement, the use of GO-POSS is an efficient strategy to slow down physical aging. The MMM at a filler loading of 0.75 wt% showed less than half of the reduction in CO2 permeability than the neat PIM-1 membrane 160 days after preparation (26% for the MMM vs 58% for the purely polymeric one). © 2022 The Author(s