The Nature of the Knowledge Base of Adult Education: The Example of Adult Education Participation

Adult educators have yet to consider the value of borrowing knowledge from other disciplines. . .tunnel vision exists

Thaxtomin A affects CESA-complex density, expression of cell wall genes, cell wall composition, and causes ectopic lignification in Arabidopsis thaliana seedlings

Thaxtomin A, a phytotoxin produced by Streptomyces eubacteria, is suspected to act as a natural cellulose synthesis inhibitor. This view is confirmed by the results obtained from new chemical, molecular, and microscopic analyses of Arabidopsis thaliana seedlings treated with thaxtomin A. Cell wall analysis shows that thaxtomin A reduces crystalline cellulose, and increases pectins and hemicellulose in the cell wall. Treatment with thaxtomin A also changes the expression of genes involved in primary and secondary cellulose synthesis as well as genes associated with pectin metabolism and cell wall remodelling, in a manner nearly identical to isoxaben. In addition, it induces the expression of several defence-related genes and leads to callose deposition. Defects in cellulose synthesis cause ectopic lignification phenotypes in A. thaliana, and it is shown that lignification is also triggered by thaxtomin A, although in a pattern different from isoxaben. Spinning disc confocal microscopy further reveals that thaxtomin A depletes cellulose synthase complexes from the plasma membrane and results in the accumulation of these particles in a small microtubule-associated compartment. The results provide new and clear evidence for thaxtomin A having a strong impact on cellulose synthesis, thus suggesting that this is its primary mode of action

Regulation of LRRK2 Stability by the E3 Ubiquitin Ligase CHIP

Dominantly inherited mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common cause of familial Parkinson's disease (PD) and have also been identified in individuals with sporadic PD. Although the exact cellular function of LRRK2 remains unknown, most PD-linked mutations appear to be toxic to cells in culture via mechanisms that depend on the kinase activity of LRRK2 or on the formation of cytoplasmic inclusions. Here we show that the E3 ubiquitin ligase CHIP physically associates with LRRK2 and regulates the cellular abundance of LRRK2. We further show that LRRK2 forms a complex with overexpressed and endogenous CHIP and Hsp90. Our data indicates that the destabilization of LRRK2 by CHIP is due to ubiquitination and proteasome-dependent degradation. Hsp90 can attenuate CHIP-mediated degradation and this can be blocked by the Hsp90 inhibitor geldanamycin. These findings provide important insight into the cellular regulation of LRRK2 stability and may lead to the development of therapeutics to treat PD based on controlling LRRK2 stability

Influence of shear-thinning blood rheology on the laminar-turbulent transition over a backward facing step

Cardiovascular diseases are the leading cause of death globally and there is an unmet need for effective, safer blood-contacting devices, including valves, stents and artificial hearts. In these, recirculation regions promote thrombosis, triggering mechanical failure, neurological dysfunction and infarctions. Transitional flow over a backward facing step is an idealised model of these flow conditions; the aim was to understand the impact of non-Newtonian blood rheology on modelling this flow. Flow simulations of shear-thinning and Newtonian fluids were compared for Reynolds numbers ( R e ) covering the comprehensive range of laminar, transitional and turbulent flow for the first time. Both unsteady Reynolds Averaged Navier–Stokes ( k − ω SST) and Smagorinsky Large Eddy Simulations (LES) were assessed; only LES correctly predicted trends in the recirculation zone length for all R e . Turbulent-transition was assessed by several criteria, revealing a complex picture. Instantaneous turbulent parameters, such as velocity, indicated delayed transition: R e = 1600 versus R e = 2000, for Newtonian and shear-thinning transitions, respectively. Conversely, when using a Re defined on spatially averaged viscosity, the shear-thinning model transitioned below the Newtonian. However, recirculation zone length, a mean flow parameter, did not indicate any difference in the transitional Re between the two. This work shows a shear-thinning rheology can explain the delayed transition for whole blood seen in published experimental data, but this delay is not the full story. The results show that, to accurately model transitional blood flow, and so enable the design of advanced cardiovascular devices, it is essential to incorporate the shear-thinning rheology, and to explicitly model the turbulent eddies

Interprofessional Communication of Clinicians Using a Mobile Phone App: A Randomized Crossover Trial Using Simulated Patients

Background: Most hospitals use paging systems as the principal communication system, despite general dissatisfaction by end users. To this end, we developed an app-based communication system (called Hark) to facilitate and improve the quality of interpersonal communication. Objective: The objectives of our study were (1) to assess the quality of information transfer using pager- and app-based (Hark) communication systems, (2) to determine whether using mobile phone apps for escalation of care results in additional delays in communication, and (3) to determine how end users perceive mobile phone apps as an alternative to pagers. Methods: We recruited junior (postgraduate year 1 and 2) doctors and nurses from a range of specialties and randomly assigned them to 2 groups who used either a pager device or the mobile phone-based Hark app. We asked nurses to hand off simulated patients while doctors were asked to receive handoff information using these devices. The quality of information transfer, time taken to respond to messages, and users’ satisfaction with each device was recorded. Each participant used both devices with a 2-week washout period in between uses. Results: We recruited 22 participants (13 nurses, 9 doctors). The quality of the referrals made by nurses was significantly better when using Hark (Hark median 118, range 100–121 versus pager median 77, range 39–104; P=.001). Doctors responded to messages using Hark more quickly than when responding to pagers, although this difference was not statistically significant (Hark mean 86.6 seconds, SD 96.2 versus pager mean 136.5 seconds, SD 201.0; P=.12). Users rated Hark as significantly better on 11 of the 18 criteria of an information transfer device (P<.05) These included “enhances interprofessional efficiency,” “results in less disturbance,” “performed desired functions reliably,” and “allows me to clearly transfer information.” Conclusions: Hark improved the quality of transfer of information about simulated patients and was rated by users as more effective and efficient, and less distracting than pagers. Using this device did not result in delay in patient care

Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field still needs to rely on a 50-y-old laborious and time-consuming method to assess the lifespan of yeast cells and to isolate differentially aged cells for microscopic snapshots via manual dissection of daughter cells from the larger mother cell. Here, we are unique in achieving continuous and high-resolution microscopic imaging of the entire replicative lifespan of single yeast cells. Our microfluidic dissection platform features an optically prealigned single focal plane and an integrated array of soft elastomer-based micropads, used together to allow for trapping of mother cells, removal of daughter cells, monitoring gradual changes in aging, and unprecedented microscopic imaging of the whole aging process. Using the platform, we found remarkable age-associated changes in phenotypes (e.g., that cells can show strikingly differential cell and vacuole morphologies at the moment of their deaths), indicating substantial heterogeneity in cell aging and death. We envision the microfluidic dissection platform to become a major tool in aging research.

Solvent Mediated Assembly of Nanoparticles Confined in Mesoporous Alumina

The controlled self-assembly of thiol stabilized gold nanocrystals in a mediating solvent and confined within mesoporous alumina was probed in situ with small angle x-ray scattering. The evolution of the self-assembly process was controlled reversibly via regulated changes in the amount of solvent condensed from an undersaturated vapor. Analysis indicated that the nanoparticles self-assembled into cylindrical monolayers within the porous template. Nanoparticle nearest-neighbor separation within the monolayer increased and the ordering decreased with the controlled addition of solvent. The process was reversible with the removal of solvent. Isotropic clusters of nanoparticles were also observed to form temporarily during desorption of the liquid solvent and disappeared upon complete removal of liquid. Measurements of the absorption and desorption of the solvent showed strong hysteresis upon thermal cycling. In addition, the capillary filling transition for the solvent in the nanoparticle-doped pores was shifted to larger chemical potential, relative to the liquid/vapor coexistence, by a factor of 4 as compared to the expected value for the same system without nanoparticles.Comment: 9 pages, 9 figures, appeared in Phys. Rev.

Monitoring dynamics of single-cell gene expression over multiple cell cycles

Recent progress in reconstructing gene regulatory networks has established a framework for a quantitative description of the dynamics of many important cellular processes. Such a description will require novel experimental techniques that enable the generation of time-series data for the governing regulatory proteins in a large number of individual living cells. Here, we utilize microfabrication to construct a Tesla microchemostat that permits single-cell fluorescence imaging of gene expression over many cellular generations. The device is used to capture and constrain asymmetrically dividing or motile cells within a trapping region and to deliver nutrients and regulate the cellular population within this region. We illustrate the operation of the microchemostat with Saccharomyces cerevisiae and explore the evolution of single-cell gene expression and cycle time as a function of generation. Our findings highlight the importance of novel assays for quantifying the dynamics of gene expression and cellular growth, and establish a methodology for exploring the effects of gene expression on long-term processes such as cellular aging