Drosophila RecQ4 Is Directly Involved in Both DNA Replication and the Response to UV Damage in S2 Cells.

The RecQ4 protein shows homology to both the S.cerevisiae DNA replication protein Sld2 and the DNA repair related RecQ helicases. Experimental data also suggest replication and repair functions for RecQ4, but the precise details of its involvement remain to be clarified.Here we show that depletion of DmRecQ4 by dsRNA interference in S2 cells causes defects consistent with a replication function for the protein. The cells show reduced proliferation associated with an S phase block, reduced BrdU incorporation, and an increase in cells with a subG1 DNA content. At the molecular level we observe reduced chromatin association of DNA polymerase-alpha and PCNA. We also observe increased chromatin association of phosphorylated H2AvD--consistent with the presence of DNA damage and increased apoptosis.Analysis of DmRecQ4 repair function suggests a direct role in NER, as the protein shows rapid but transient nuclear localisation after UV treatment. Re-localisation is not observed after etoposide or H₂O₂ treatment, indicating that the involvement of DmRecQ4 in repair is likely to be pathway specific.Deletion analysis of DmRecQ4 suggests that the SLD2 domain was essential, but not sufficient, for replication function. In addition a DmRecQ4 N-terminal deletion could efficiently re-localise on UV treatment, suggesting that the determinants for this response are contained in the C terminus of the protein. Finally several deletions show differential rescue of dsRNA generated replication and proliferation phenotypes. These will be useful for a molecular analysis of the specific role of DmRecQ4 in different cellular pathways

Towards the development of the psychosocial impact of assistive devices scale for continence (C-PIADS)

BACKGROUND: Current outcome measures for continence management devices do not adequately address psychosocial impact. The PIADS is an assessment tool that has been shown to reliably predict the adoption and use of assistive technology devices, but it is not widely used for continence devices. OBJECTIVE: To explore whether the PIADS requires modification to address the particular needs of continence device users and to inform any subsequent item development. METHODS: The study used interpretive methods in which qualitative information from semi-structured interviews was combined with the findings from cognitive interviews for questionnaire pre-testing. A total of 40 participants in UK and Canada were interviewed. RESULTS: Few participants had difficulty in understanding or relating to the majority of PIADS items. Several items were not considered relevant to continence and some areas for potential new items were uncovered. Embarrassment and concealment of urinary incontinence from others were common topics. CONCLUSIONS: The PIADS appears to fundamentally address many, but not all, of the important psychosocial concerns of adults who have continence difficulties. A version for continence, the C-PIADS, will require modification of the PIADS and is likely to contain some new items

Autonomous reconfigurable GPS/INS navigation and pointing system for rendezvous and docking

This paper describes the results of an integrated navigation and pointing system software development effort sponsored by the NASA MSFC through a SBIR Phase 2 Program. The integrated Global Positioning System (GPS)/Inertial Navigation System (INS) implements an autonomous navigation filter that is reconfigurable in real-time to accommodate mission contingencies. An onboard expert system monitors the spacecraft status and reconfigures the navigation filter accordingly, to optimize the system performance. The navigation filter is a multi-mode Kalman filter to estimate the spacecraft position, velocity, and attitude. Three different GPS-based attitude determination techniques, namely, velocity vector matching, attitude vector matching, and interferometric processing, are implemented to encompass different mission contingencies. The integrated GPS/INS navigation filter will use any of these techniques depending on the mission phase and the state of the sensors. The first technique, velocity vector matching, uses the GPS velocity measurement to estimate the INS velocity errors and exploits the correlation between INS velocity and attitude errors to estimate the attitude. The second technique, attitude vector matching, uses INS gyro measurements and GPS carrier phase (integrated Doppler) measurements during a spacecraft rotation maneuver to determine the attitude. Both of these techniques require only one GPS antenna onboard to determine the spacecraft attitude. The third technique, interferometric processing, requires use of multiple GPS antennae. In order to determine 3-axis body attitude, three GPS antennae (2 no-coplanor baselines) are required

Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation.

Both Mcm10 and HP1a are known to be required for DNA replication. However, underlying mechanism is not clarified yet especially for HP1. Knockdown of both HP1a and Mcm10 genes inhibited the progression of S phase in Drosophila eye imaginal discs. Proximity Ligation Assay (PLA) demonstrated that HP1a is in close proximity to DNA replication proteins including Mcm10, RFC140 and DNA polymerase ε 255 kDa subunit in S-phase. This was further confirmed by co-immunoprecipitation assay. The PLA signals between Mcm10 and HP1a are specifically observed in the mitotic cycling cells, but not in the endocycling cells. Interestingly, many cells in the posterior regions of eye imaginal discs carrying a double knockdown of Mcm10 and HP1a induced ectopic DNA synthesis and DNA damage without much of ectopic apoptosis. Therefore, the G1-S checkpoint may be affected by knockdown of both proteins. This event was also the case with other HP family proteins such as HP4 and HP6. In addition, both Mcm10 and HP1a are required for differentiation of photoreceptor cells R1, R6 and R7. Further analyses on several developmental genes involved in the photoreceptor cell differentiation suggest that a role of both proteins is mediated by regulation of the lozenge gene

What are the participants’ perspectives of taking melatonin for the treatment of nocturia in Multiple Sclerosis? -a qualitative study embedded within a double blind RCT

Background: Multiple Sclerosis (MS) is a chronic neurological disorder caused by neurodegeneration within the central nervous system. It results in impaired physical, cognitive and psychological functioning and can also lead to lower urinary tract symptoms including nocturia. While clinical trials have suggested an association between nocturia and melatonin secretion, to our knowledge, no qualitative research has been conducted on the experience of taking melatonin to treat nocturia in progressive MS within a clinical trial. Methods: 17 semi-structured qualitative interviews were conducted as part of a double-blind, randomised, placebo controlled, crossover, clinical trial with consenting adults with MS. Interviews explored participants’ experiences of nocturia associated with MS and their experience of taking melatonin as a trial treatment for nocturia versus a placebo. Data was analysed using a thematic analysis. Results: Themes on the experience of nocturia revealed participants’ understandings of nocturia, the impact it had on their night and increased daily fatigue. Themes on the intervention showed perceived improvements to nocturia, sleep and energy and negative effects including lethargy, a lack of significant change and physical side effects including vivid dreams.Conclusion: This qualitative exploration revealed an association between nocturia and increased levels of fatigue during the day by those with MS. However, perspectives towards the effectiveness of melatonin as a potential treatment varied as both placebo and melatonin were perceived as having very similar effects

A 500 year sediment lake record of anthropogenic and natural inputs to Windermere (English Lake District) using double-spike lead isotopes, radiochronology, and sediment microanalysis

A high-resolution record of pollution is preserved in recent sediments from Windermere, the largest lake in the English Lake District. Data derived from X-ray core scanning (validated against wavelength dispersive X-ray fluorescence), radiochronological techniques (210Pb and 137Cs) and ultrahigh precision, double-spike mass spectrometry for lead isotopes are combined to decipher the anthropogenic inputs to the lake. The sediment record suggests that while most element concentrations have been stable, there has been a significant increase in lead, zinc, and copper concentrations since the 1930s. Lead isotope down-core variations identify three major contributory sources of anthropogenic (industrial) lead, comprising gasoline lead, coal combustion lead (most likely source is coal-fired steam ships), and lead derived from Carboniferous Pb–Zn mineralization (mining activities). Periods of metal workings do not correlate with peaks in heavy metals due to the trapping efficiency of up-system lakes in the catchment. Heavy metal increases could be due to flood-induced metal inwash after the cessation of mining and the weathering of bedrock in the catchment. The combination of sediment analysis techniques used provides new insights into the pollutant depositional history of Windermere and could be similarly applied to other lake systems to determine the timing and scale of anthropogenic inputs

Socio-economic utility and chemical potential

In statistical physics, the conservation of particle number results in the equalization of the chemical potential throughout a system at equilibrium. In contrast, the homogeneity of utility in socio-economic models is usually thought to rely on the competition between individuals, leading to Nash equilibrium. We show that both views can be reconciled by introducing a notion of chemical potential in a wide class of socio-economic models, and by relating it in a direct way to the equilibrium value of the utility. This approach also allows the dependence of utility across the system to be determined when agents take decisions in a probabilistic way. Numerical simulations of a urban economic model also suggest that our result is valid beyond the initially considered class of solvable models.Comment: 6 pages, 3 figures, final versio

When asking ‘what’ and ‘how’ helps you win: mimicry of interrogative terms facilitates successful online negotiations

Strategic word mimicry during negotiations facilitates better outcomes. We explore mimicry of specific word categories and perceptions of rapport, trust, and liking as underlying mechanisms. Dyads took part in an online negotiation exercise in which word mimicry was manipulated: participants were instructed to mimic each other’s words (both-mimic), one participant mimicked the other (half-mimic) or neither participant mimicked (neither-mimic). When given a simple instruction to mimic their partner, participants mimicked both the style (personal pronouns, adverbs, linguistic style, interrogative terms) and the content (affiliation terms, power terms, and assents) of their partner’s messages. Mimicry was associated with greater joint and individual points gain and perceptions of rapport from the mimicked partner. Further, mimicry of interrogative terms (e.g., how, why) mediated positive effects of mimicry upon negotiation outcomes, suggesting the coordination of question asking between negotiators is an important strategy to create beneficial interactions and add value in negotiations