Synaptic-like vesicles and candidate transduction channels in mechanosensory terminals

Acknowledgements I would like to thank the Medical Research Council for funding our work from 2007 to 2010 (G0601253), SULSA and Eli Lilly for support to Sonia Watson from 2010 to 2014, and Tenovus Scotland for current support to Karen Thompson.Peer reviewedPublisher PD

Developing librarians as teachers: A study of their pedagogical knowledge

The widespread involvement of librarians in information literacy education has raised concerns about their development as teachers, but there is little research on their acquisition and application of pedagogical knowledge. A questionnaire was used to collect mainly quantitative data about the teaching roles, pedagogical knowledge and professional development of subject librarians in 82 UK higher education institutions. Two expert interviews and a literature review informed the design and contextualized the findings. The survey showed postholders were engaged in a variety of teaching-related activities, regarded as central to their work. Contrary to assumptions, most felt confident about teaching and thought their knowledge sufficient, giving examples of pedagogical theory gained via courses informing their teaching practice. Although on-the-job development was common, the majority had undertaken a short course and/or extended programme. Respondents favoured incorporating a teaching module into initial professional education and providing tailored programmes for librarians with substantial teaching roles. © The Author(s) 2010

The Influence of Formulation, Buffering, pH and Divalent Cations on the Activity of Endothall on Hydrilla.

Endothall has been used as an aquatic herbicide for more than 40 years and provides very effective weed control of many weeds. Early research regarding the mechanism-of-action of endothall contradicts the symptomology normally associated with the product. Recent studies suggest endothall is a respiratory toxin but the mechanism-of-action remains unknown. To further elucidate the activity of endothall, several endothall formulations were evaluated for their effects on ion leakage, oxygen consumption and photosynthetic oxygen evolution from hydrilla shoot tips. The influence of pH, buffering and divalent cations was also evaluated. (PDF contains 6 pages.

Mathematical model of Zika virus with vertical transmission

Zika is a flavivirus transmitted to humans through either the bites of infected Aedes mosquitoes or sexual transmission. Zika has been linked to congenital anomalies such as microcephaly. In this paper, we analyze a new system of ordinary differential equations which incorporates human vertical transmission of Zika virus, the birth of babies with microcephaly and asymptomatically infected individuals. The Zika model is locally and globally asymptotically stable when the basic reproduction number is less than unity. Our model shows that asymptomatic individuals amplify the disease burden in the community, and the most important parameters for ZIKV spread are the death rate of mosquitoes, the mosquito biting rate, the mosquito recruitment rate, and the transmission per contact to mosquitoes and to adult humans. Scenario exploration indicates that personal-protection is a more effective control strategy than mosquito-reduction strategy. It also shows that delaying conception reduces the number of microcephaly cases, although this does little to prevent Zika transmission in the broader community. However, by coupling aggressive vector control and personal protection use, it is possible to reduce both microcephaly and Zika transmission. 2000 Mathematics Subject Classifications: 92B05, 93A30, 93C15

Modelling the mechanoreceptor’s dynamic behaviour

All sensory receptors adapt, i.e. they constantly adjust their sensitivity to external stimuli to match the current demands of the natural environment. Electrophysiological responses of sensory receptors from widely different modalities seem to exhibit common features related to adaptation, and these features can be used to examine the underlying sensory transduction mechanisms. Among the principal senses, mechanosensation remains the least understood at the cellular level. To gain greater insights into mechanosensory signalling, we investigated if mechanosensation displayed adaptive dynamics that could be explained by similar biophysical mechanisms in other sensory modalities. To do this, we adapted a fly photoreceptor model to describe the primary transduction process for a stretch-sensitive mechanoreceptor, taking into account the viscoelastic properties of the accessory muscle fibres and the biophysical properties of known mechanosensitive channels (MSCs). The model's output is in remarkable agreement with the electrical properties of a primary ending in an isolated decapsulated spindle; ramp-and-hold stretch evokes a characteristic pattern of potential change, consisting of a large dynamic depolarization during the ramp phase and a smaller static depolarization during the hold phase. The initial dynamic component is likely to be caused by a combination of the mechanical properties of the muscle fibres and a refractory state in the MSCs. Consistent with the literature, the current model predicts that the dynamic component is due to a rapid stress increase during the ramp. More novel predictions from the model are the mechanisms to explain the initial peak in the dynamic component. At the onset of the ramp, all MSCs are sensitive to external stimuli, but as they become refractory (inactivated), fewer MSCs are able to respond to the continuous stretch, causing a sharp decrease after the peak response. The same mechanism could contribute a faster component in the ‘sensory habituation’ of mechanoreceptors, in which a receptor responds more strongly to the first stimulus episode during repetitive stimulation

Identifying professionals' needs in integrating electronic pain monitoring in community palliative care services: an interview study

Background: Poor pain assessment is a barrier to effective pain control. There is growing interest internationally in the development and implementation of remote monitoring technologies to enhance assessment in cancer and chronic disease contexts. Findings describe the development and testing of pain monitoring systems but research identifying the needs of health professionals to implement routine monitoring systems within clinical practice is limited. Aim: To inform the development and implementation strategy of an electronic pain monitoring system, PainCheck, by understanding palliative care professionals’ needs when integrating PainCheck into routine clinical practice. Design: Qualitative study using face-to-face interviews. Data were analysed using framework analysis Setting/participants: Purposive sample of health professionals managing the palliative care of patients living in the community Results: Fifteen interviews with health professionals took place. Three meta-themes emerged from the data: 1) Uncertainties about integration of PainCheck and changes to current practice; 2) Appraisal of current practice; 3) Pain management is everybody’s responsibility Conclusions: Even the most sceptical of health professionals could see the potential benefits of implementing an electronic patient-reported pain monitoring system. Health professionals have reservations about how PainCheck would work in practice. For optimal use PainCheck needs embedding within existing electronic health records. Electronic pain monitoring systems have the potential to enable professionals to support patients’ pain management more effectively but only when barriers to implementation are appropriately identified and addressed

Charge fluctuations and electron-phonon coupling in organic charge-transfer salts with neutral-ionic and Peierls transitions

The first-order transition of the charge-transfer complex TTF-CA (tetrathiafulvalene-chloranil) is both a neutral-ionic and a Peierls transition. In related organic charge transfer complexes, cooling at ambient pressure increases the ionicity $\rho$ in strikingly different ways, and is sometimes accompanied by a dielectric peak, that we relate to lattice stiffness, to structural and energetic disorder, and to the softening of the Peierls mode in the far-IR. The position operator $P$ for systems with periodic boundary conditions makes possible a systematic treatment of electron-phonon interactions in extended donor-acceptor stacks in terms of correlated Peierls-Hubbard models. The IR intensity of the Peierls mode peaks at the Peierls transition at small $\rho < 1/2$ in soft lattices, where the dielectric constant also has a large peak. In dimerized stacks, the IR intensity of totally symmetric, Raman active, molecular vibrations is related to charge fluctuations that modulate site energies. Combination bands of molecular and Peierls modes are identified in regular TTF-CA stacks above Tc. Energetic disorder can suppress the Peierls transition and rationalize a continuous crossover from small to large $\rho$. The TTF-CA scenario of a neutral-regular to ionic-dimerized transition must be broadened considerably in view of charge transfer salts that dimerize on the neutral side, that become ionic without a structural change, or that show vibrational evidence for dimerization at constant $\rho < 1$.Comment: 26 pages including figure

Importance of Full-Collapse Vesicle Exocytosis for Synaptic Fatigue-Resistance at Rat Fast and Slow Muscle Neuromuscular Junctions

We would like to thank Dr Robert Banks, Prof Arild Njå and Prof Bill Wisden and Dr Phil Sheard for their helpful comments and discussions during the preparation of this manuscript, as well as for the contributions made by undergraduate students Alison Cuthbert, Richard McWilliam and Karen Peters, who helped produce initial observations prompting this study. This work was supported by grants from the Biotechnology and Biological Science Research Council of the UK (BBSRC-1/511921) and The Wellcome Trust (WT-057994/2/99/Z).Peer reviewedPublisher PD

The role of depletion of dimethyl sulfoxide before autografting: on hematologic recovery, side effects, and toxicity

AbstractCryopreservation of stem cells after collection from peripheral blood or bone marrow for autologous transplantation necessitates protection with dimethyl sulfoxide (DMSO). Unfortunately, DMSO, when infused with the thawed cell suspension, may induce serious complications and side effects. To assess whether depletion of DMSO before autografting affects safety and efficacy, 56 consenting consecutive patients treated with high-dose chemotherapy and autologous blood stem cell transplantation were assigned to obtain either an untreated or DMSO-depleted autograft. On the day of transplantation, the cryopreserved cells were thawed and infused to the patient either immediately or after washing 3 times in normal saline supplemented with 6% anticoagulant citrate dextrose solution. Cell count with viability, clonogenic assay, and phenotyping were performed before and after thawing and after washing. Hematologic recovery, side effects, and complications were recorded. The in vitro and clinical data on 56 patients show that the depletion of DMSO in vitro before autografting does not induce a significant loss of cell number, viability, colony-forming unit-granulocyte-macrophage activity, or number of CD34+ cells. Furthermore, it leads to a safe and sustained engraftment. The complications and side effects, as recorded by continuous monitoring, were substantially less; however, the procedure takes 3 to 4 hours of laboratory work per patient

Mechanotransduction channels in proprioceptive sensory nerve terminals: still an open question?

Mechanosensory transduction (MST) in proprioceptors, and other low threshold mechanosensory nerve terminals (LTMT), has been debated intensely for decades. MST in muscle spindles produces a receptor potential that encodes stimulus speed and duration, is predominantly due to Na+, a little Ca2+, plus some transient, non-mechanically-gated K+ ion fluxes. The abundant, multiple Na+-selective DEG/ENaC channel isoforms present in all LTMTs seemed obvious Na+ sources, perhaps supplemented with Ca2+-selective TRPs, and Ca2+-activated K+ channels. However, genetic deletions of even multiple DEG/ENaC genes produces only mild functional perturbation. Conversely, deleting the more recently discovered Piezo2 mechanosensory protein profoundly impairs LTMT responses, including in muscle spindles. Yet, its transient opening, non-Na+-selectivity and pharmacology do not reflect known receptor potential and response properties. A Ca2+-dependent recycling vesicle pool that we have shown is essential for mechanosensitivity, plus other recent DEG/ENaC discoveries, may reconcile these conflicting observations. We propose the abundance of axolemmal MST complexes, comprising untested DEG/ENaC combinations, is controlled by Piezo2-gated Ca2+ influx that regulates their vesicular insertion and retrieval