Molecular mechanisms regulating formation, trafficking and processing of annular gap junctions

Internalization of gap junction plaques results in the formation of annular gap junction vesicles. The factors that regulate the coordinated internalization of the gap junction plaques to form annular gap junction vesicles, and the subsequent events involved in annular gap junction processing have only relatively recently been investigated in detail. However it is becoming clear that while annular gap junction vesicles have been demonstrated to be degraded by autophagosomal and endo-lysosomal pathways, they undergo a number of additional processing events. Here, we characterize the morphology of the annular gap junction vesicle and review the current knowledge of the processes involved in their formation, fission, fusion, and degradation. In addition, we address the possibility for connexin protein recycling back to the plasma membrane to contribute to gap junction formation and intercellular communication. Information on gap junction plaque removal from the plasma membrane and the subsequent processing of annular gap junction vesicles is critical to our understanding of cell-cell communication as it relates to events regulating development, cell homeostasis, unstable proliferation of cancer cells, wound healing, changes in the ischemic heart, and many other physiological and pathological cellular phenomena

Clarifying the relationship between metformin, acute kidney injury and lactic acidosis

No abstract available

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

Gene silencing in tick cell lines using small interfering or long double-stranded RNA

Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system

Stellar Disk Truncations: Where do we stand ?

In the light of several recent developments we revisit the phenomenon of galactic stellar disk truncations. Even 25 years since the first paper on outer breaks in the radial light profiles of spiral galaxies, their origin is still unclear. The two most promising explanations are that these 'outer edges' either trace the maximum angular momentum during the galaxy formation epoch, or are associated with global star formation thresholds. Depending on their true physical nature, these outer edges may represent an improved size characteristic (e.g., as compared to D_25) and might contain fossil evidence imprinted by the galaxy formation and evolutionary history. We will address several observational aspects of disk truncations: their existence, not only in normal HSB galaxies, but also in LSB and even dwarf galaxies; their detailed shape, not sharp cut-offs as thought before, but in fact demarcating the start of a region with a steeper exponential distribution of starlight; their possible association with bars; as well as problems related to the line-of-sight integration for edge-on galaxies (the main targets for truncation searches so far). Taken together, these observations currently favour the star-formation threshold model, but more work is necessary to implement the truncations as adequate parameters characterising galactic disks.Comment: LaTeX, 10 pages, 6 figures, presented at the "Penetrating Bars through Masks of Cosmic Dust" conference in South Africa, proceedings published by Kluwer, and edited by Block, D.L., Freeman, K.C., Puerari, I., & Groess, R; v3 to match published versio

Motivational interviewing for low mood and adjustment early after stroke: a feasibility randomised trial

Background Management of psychological adjustment and low mood after stroke can result in positive health outcomes. We have adapted a talk-based therapy, motivational interviewing (MI), and shown it to be potentially effective for managing low mood and supporting psychological adjustment post-stroke in a single-centre trial. In the current study, we aimed to explore the feasibility of delivering MI using clinical stroke team members, and using an attention control (AC), to inform the protocol for a future definitive trial. Methods This parallel two-arm feasibility trial took place in north-west England. Recruitment occurred between December 2012 and November 2013. Participants were stroke patients aged 18 years or over, who were medically stable, had no severe communication problems, and were residents of the hospital catchment. Randomisation was to MI or AC, and was conducted by a researcher not involved in recruitment using opaque sealed envelopes. The main outcome measures were descriptions of study feasibility (recruitment/retention rates, MI delivery by clinical staff, use of AC) and acceptability (through qualitative interviews and completion of study measures), and fidelity to MI and AC (through review of session audio-recordings). Information was also collected on participants’ mood, quality of life, adjustment, and resource-use. Results Over 12 months, 461 patients were screened, 124 were screened eligible, and 49 were randomised: 23 to MI, 26 to AC. At 3 months, 13 MI and 18 AC participants completed the follow-up assessment (63% retention). This was less than expected based on our original trial. An AC was successfully implemented. Alternative approaches would be required to ensure the feasibility of clinical staff delivering MI. The study measures, MI, and AC interventions were considered acceptable, and there was good fidelity to the interventions. There were no adverse events related to study participation. Conclusions It was possible to recruit and retain participants, train clinical staff to deliver MI, and implement an appropriate AC. Changes would be necessary to conduct a future multi-centre trial, including: assuming a recruitment rate lower than that in the current study; implementing more strategies to increase participant retention; and considering alternative clinical staff groups to undertake the delivery of MI and AC

Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected

Mapping species distributions: A comparison of skilled naturalist and lay citizen science recording

To assess the ability of traditional biological recording schemes and lay citizen science approaches to gather data on species distributions and changes therein, we examined bumblebee records from the UK’s national repository (National Biodiversity Network) and from BeeWatch. The two recording approaches revealed similar relative abundances of bumblebee species but different geographical distributions. For the widespread common carder (Bombus pascuorum), traditional recording scheme data were patchy, both spatially and temporally, reflecting active record centre rather than species distribution. Lay citizen science records displayed more extensive geographic coverage, reflecting human population density, thus offering better opportunities to account for recording effort. For the rapidly spreading tree bumblebee (Bombus hypnorum), both recording approaches revealed similar distributions due to a dedicated mapping project which overcame the patchy nature of naturalist records. We recommend, where possible, complementing skilled naturalist recording with lay citizen science programmes to obtain a nation-wide capability, and stress the need for timely uploading of data to the national repository