MicroRNA-330-5p as a putative modulator of neoadjuvant chemoradiotherapy sensitivity in oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of miR-330-5p as a predictive biomarker of patient sensitivity to neo-CRT and as a novel therapeutic target for manipulating cellular sensitivity to neo-CRT in patients with OAC

'I would rather die': reasons given by 16-year-olds for not continuing their study of mathematics

Improving participation rates in specialist mathematics after the subject ceases to be compulsory at age 16 is part of government policy in England. This article provides independent and recent support for earlier findings concerning reasons for non- participation, based on free response and closed items in a questionnaire with a sample of over 1500 students in 17 schools, close to the moment of choice. The analysis supports findings that perceived difficulty and lack of confidence are important reasons for students not continuing with mathematics, and that perceived dislike and boredom, and lack of relevance, are also factors. There is a close relationship between reasons for non-participation and predicted grade, and a weaker relation to gender. An analysis of the effects of schools, demonstrates that enjoyment is the main factor differentiating schools with high and low participation indices. Building on discussion of these findings, ways of improving participation are briefly suggested

A downward revision to the distance of the 1806-20 cluster and associated magnetar from Gemini near-Infrared spectroscopy

We present H- and K-band spectroscopy of OB and Wolf-Rayet (WR) members of the Milky Way cluster 1806-20 (G10.0-0.3), to obtain a revised cluster distance of relevance to the 2004 giant flare from the SGR 1806-20 magnetar. From GNIRS spectroscopy obtained with Gemini South, four candidate OB stars are confirmed as late O/early B supergiants, while we support previous mid WN and late WC classifications for two WR stars. Based upon an absolute Ks-band magnitude calibration for B supergiants and WR stars, and near-IR photometry from NIRI at Gemini North plus archival VLT/ISAAC datasets, we obtain a cluster distance modulus of 14.7+/-0.35 mag. The known stellar content of the 1806-20 cluster suggests an age of 3-5 Myr, from which theoretical isochrone fits infer a distance modulus of 14.7+/-0.7 mag. Together, our results favour a distance modulus of 14.7+/-0.4 mag (8.7^+1.8_-1.5 kpc) to the 1806-20 cluster, which is significantly lower than the nominal 15 kpc distance to the magnetar. For our preferred distance, the peak luminosity of the December 2004 giant flare is reduced by a factor of three to 7 X 10^46 erg/s, such that the contamination of BATSE short gamma ray bursts (GRB's) from giant flares of extragalactic magnetars is reduced to a few percent. We infer a magnetar progenitor mass of ~48^+20_-8 Msun, in close agreement with that obtained recently for the magnetar in Westerlund 1.Comment: 6 pages, 4 figures, accepted for MNRAS Letter

Shift in the microbial ecology of a hospital hot water system following the introduction of an on-site monochloramine disinfection system

Drinking water distribution systems, including premise plumbing, contain a diverse microbiological community that may include opportunistic pathogens. On-site supplemental disinfection systems have been proposed as a control method for opportunistic pathogens in premise plumbing. The majority of on-site disinfection systems to date have been installed in hospitals due to the high concentration of opportunistic pathogen susceptible occupants. The installation of on-site supplemental disinfection systems in hospitals allows for evaluation of the impact of on-site disinfection systems on drinking water system microbial ecology prior to widespread application. This study evaluated the impact of supplemental monochloramine on the microbial ecology of a hospital's hot water system. Samples were taken three months and immediately prior to monochloramine treatment and monthly for the first six months of treatment, and all samples were subjected to high throughput Illumina 16S rRNA region sequencing. The microbial community composition of monochloramine treated samples was dramatically different than the baseline months. There was an immediate shift towards decreased relative abundance of Betaproteobacteria, and increased relative abundance of Firmicutes, Alphaproteobacteria, Gammaproteobacteria, Cyanobacteria and Actinobacteria. Following treatment, microbial populations grouped by sampling location rather than sampling time. Over the course of treatment the relative abundance of certain genera containing opportunistic pathogens and genera containing denitrifying bacteria increased. The results demonstrate the driving influence of supplemental disinfection on premise plumbing microbial ecology and suggest the value of further investigation into the overall effects of premise plumbing disinfection strategies on microbial ecology and not solely specific target microorganisms. © 2014 Baron et al

Effect of magnetic state on the γ−α\gamma -\alpha transition in iron: First-principle calculations of the Bain transformation path

Energetics of the fcc ($\gamma$) - bcc ($\alpha$) lattice transformation by the Bain tetragonal deformation is calculated for both magnetically ordered and paramagnetic (disordered local moment) states of iron. The first-principle computational results manifest a relevance of the magnetic order in a scenario of the $\gamma$ - $\alpha$ transition and reveal a special role of the Curie temperature of $\alpha$-Fe, $T_C$, where a character of the transformation is changed. At a cooling down to the temperatures $T < T_C$ one can expect that the transformation is developed as a lattice instability whereas for $T > T_C$ it follows a standard mechanism of creation and growth of an embryo of the new phase. It explains a closeness of $T_C$ to the temperature of start of the martensitic transformation, $M_s$.Comment: 4 pages, 3 figures, submitted in Phys. Rev. Letter

Plants lacking the main light-harvesting complex retain photosystem II macro-organization

Photosystem II (PSII) is a key component of photosynthesis, the process of converting sunlight into the chemical energy of life. In plant cells, it forms a unique oligomeric macrostructure in membranes of the chloroplasts. Several light-harvesting antenna complexes are organized precisely in the PSII macrostructure—the major trimeric complexes (LHCII) that bind 70% of PSII chlorophyll and three minor monomeric complexes—which together form PSII supercomplexes. The antenna complexes are essential for collecting sunlight and regulating photosynthesis, but the relationship between these functions and their molecular architecture is unresolved. Here we report that antisense Arabidopsis plants lacking the proteins that form LHCII trimers have PSII supercomplexes with almost identical abundance and structure to those found in wild-type plants. The place of LHCII is taken by a normally minor and monomeric complex, CP26, which is synthesized in large amounts and organized into trimers. Trimerization is clearly not a specific attribute of LHCII. Our results highlight the importance of the PSII macrostructure: in the absence of one of its main components, another protein is recruited to allow it to assemble and function

A study of decomposition methods for refinement of H + -ZSM5 zeolite with powder diffraction data

Abstract. Profile and integrated intensity decomposition refinements have been carried out on H+ -ZSM5 X-ray powder diffractometer data (110 structural parameters). This compound is a zeolite catalyst. The Si04 tetrahedra were constrained towards regularity. Chemically sensible results and good fits between observed and calculated profiles and integrated intensities were obtained. It is concluded that larger structures (100-150 structural variables) can be refined from conventional X-ray powder diffractometer data with either of these methods if appropriate geometrical constraints are applied

Around the tangent cone theorem

A cornerstone of the theory of cohomology jump loci is the Tangent Cone theorem, which relates the behavior around the origin of the characteristic and resonance varieties of a space. We revisit this theorem, in both the algebraic setting provided by cdga models, and in the topological setting provided by fundamental groups and cohomology rings. The general theory is illustrated with several classes of examples from geometry and topology: smooth quasi-projective varieties, complex hyperplane arrangements and their Milnor fibers, configuration spaces, and elliptic arrangements.Comment: 39 pages; to appear in the proceedings of the Configurations Spaces Conference (Cortona 2014), Springer INdAM serie