The organisation and functions of local Ca²⁺ signals

Calcium (Ca2+) is a ubiquitous intracellular messenger, controlling a diverse range of cellular processes, such as gene transcription, muscle contraction and cell proliferation. The ability of a simple ion such as Ca2+ to play a pivotal role in cell biology results from the facility that cells have to shape Ca2+ signals in space, time and amplitude. To generate and interpret the variety of observed Ca2+ signals, different cell types employ components selected from a Ca2+ signalling 'toolkit', which comprises an array of homeostatic and sensory mechanisms. By mixing and matching components from the toolkit, cells can obtain Ca2+ signals that suit their physiology. Recent studies have demonstrated the importance of local Ca2+ signals in defining the specificity of the interaction of Ca2+ with its targets. Furthermore, local Ca2+ signals are the triggers and building blocks for larger global signals that propagate throughout cells

From Coach to Positive Psychology Coach

The success of positive psychology interventions and visual learning methods combined with the growing field of executive coaching provides rich opportunity to develop potentially transformative positive coaching methods. My hypothesis is that it is possible to become a deeper coach helping clients to achieve improved outcomes by understanding effective coaching methods and identifying a few specific vehicles of constructive engagement (positive interventions), developing depth and expertise as a coach in these areas, and applying these with supporting visuals to coaching engagements. This paper includes a literature review of pertinent positive psychology, coaching and visual learning research. Also, I gather a broad perspective of positive psychology constructs and successful coaching interventions by interviewing current positive psychology coaches, researchers, and visual practitioners. Findings: while each interviewee uses the breadth of positive psychology research and concepts, each seems to have a particular focus area that reflects that individual’s particular personality or interests. Therefore, I chose to focus on three particular areas of interest to me – cognitive-behavioral coaching to influence one’s internal dialogue and explanatory style, positive emotions, and visual learning. I foresee using these approaches frequently in my coaching engagements

Local and global spontaneous calcium events regulate neurite outgrowth and onset of GABAergic phenotype during neural precursor differentiation

Neural stem cells can generate in vitro progenitors of the three main cell lineages found in the CNS. The signaling pathways underlying the acquisition of differentiated phenotypes in these cells are poorly understood. Here we tested the hypothesis that Ca2+ signaling controls differentiation of neural precursors. We found low-frequency global and local Ca2+ transients occurring predominantly during early stages of differentiation. Spontaneous Ca2+ signals in individual precursors were not synchronized with Ca2+ transients in surrounding cells. Experimentally induced changes in the frequency of local Ca2+signals and global Ca2+ rises correlated positively with neurite outgrowth and the onset of GABAergic neurotransmitter phenotype, respectively. NMDA receptor activity was critical for alterations in neuronal morphology but not for the timing of the acquisition of the neurotransmitter phenotype. Thus, spontaneous Ca2+ signals are an intrinsic property of differentiating neurosphere-derived precursors. Their frequency may specify neuronal morphology and acquisition of neurotransmitter phenotype

Agricultural shows: visitor motivation, experience and behavioural intention

Purpose - This paper contributes to theory concerning visitor motivations, consumer experience and behavioural intentions at rural events; more specifically, it focuses on agricultural shows, which have hitherto been neglected in the events management literature. These events have successfully broadened their visitor base, but not without the attendant challenges for agricultural events' designers. Design/methodology/approach - The research adopts a quantitative design using a questionnaire survey. The analysis, using a range of statistical procedures, centres on consumer motivation, experience and behaviour in relation to show features and their influence on future behaviour. Findings - Demonstrate the relative importance to the consumer, of the show’s various components and their influence on revisitation, which reflect the significance of social, cultural and personal meanings attached to their experiences. This highlights key motivational variables such as appreciating the shows' traditions and intellectual enrichment Research limitations/implications - The study takes a cross sectional approach, using a non-probability sample at four multiday royal shows. Future research should establish the external validity of the findings and their applicability to smaller one day agricultural shows Practical implications - The research provides a managerial contribution by informing show designers about the motivations of an increasingly diverse range of visitors. This will facilitate decisions around the engagement of contemporary design while preserving the traditional elements of agricultural shows. Originality/value - Few studies have looked at rural events and, in particular, agricultural shows. Moreover, previous research in this area has focused on rural tourism and place making, while consumer behaviour and experience at rural events has been neglected. This paper provides an insight into the consumer experience and perceived importance of various aspects of contemporary agricultural shows

Electrochromic properties of a poly(dithienylfuran) derivative featuring a redox-active dithiin unit

A teraryl monomer containing a 1,4-dithiin-furan central unit has been synthesised and characterised by single crystal X-ray crystallography. The di(thienyl)furan monomer 11 was successfully polymerised electrochemically and shown to possess a lower electrochemical band gap than its terthiophene analogue (1.97 eV cf. 2.11 eV). The electrochromic properties of this polymer proved to be superior to PEDOT, with fast switching and reversible colour transformation at high colour contrast (CE = 212 cm(2) C-1 cf. 183 cm(2) C-1 for PEDOT at 95% optical switch)

Calcium puffs are generic InsP₃-activated elementary calcium signals and are downregulated by prolonged hormonal stimulation to inhibit cellular calcium responses

Elementary Ca2+ signals, such as "Ca2+ puffs", which arise from the activation of inositol 1,4,5-trisphosphate receptors, are building blocks for local and global Ca2+ signalling. We characterized Ca2+ puffs in six cell types that expressed differing ratios of the three inositol 1,4,5-trisphosphate receptor isoforms. The amplitudes, spatial spreads and kinetics of the events were similar in each of the cell types. The resemblance of Ca2+ puffs in these cell types suggests that they are a generic elementary Ca2+ signal and, furthermore, that the different inositol 1,4,5-trisphosphate isoforms are functionally redundant at the level of subcellular Ca2+ signalling. Hormonal stimulation of SH-SY5Y neuroblastoma cells and HeLa cells for several hours downregulated inositol 1,4,5-trisphosphate expression and concomitantly altered the properties of the Ca2+ puffs. The amplitude and duration of Ca2+ puffs were substantially reduced. In addition, the number of Ca2+ puff sites active during the onset of a Ca2+ wave declined. The consequence of the changes in Ca2+ puff properties was that cells displayed a lower propensity to trigger regenerative Ca2+ waves. Therefore, Ca2+ puffs underlie inositol 1,4,5-trisphosphate signalling in diverse cell types and are focal points for regulation of cellular responses

Neuroimaging of Vessel Amyloid in Alzheimer's Disease a , b

Despite extensive recent advances in understanding Alzheimer's disease (AD) we are unable to noninvasively establish a definite diagnosis during life and cannot monitor the cerebral deposition of amyloid Β protein (A/Β) in living patients. We evaluated the use of 10H3, a monoclonal antibody Fab targeting AΒ protein 1-28 labeled with Tc-99m. Six subjects with probable AD were studied using single-photon emission computed tomography (SPECT) at times from 0–24 hours following injection. Curves of radioactivity in blood demonstrate a half-life of the injected Fab of 2–3 hours. Images show uptake around the head in the scalp or bone marrow in all subjects. There is no evidence of cerebral uptake of the antibody. Scalp biopsies in all six patients demonstrate diffuse staining with 10H3 of the scalp, a pattern indistinguishable from that found in controls. Evidence of amyloid deposition in the scalp in AD is not seen with other anti-AΒ antibodies, suggesting that 10H3 is cross-reacting with another protein. Further studies with anti-AΒ antibodies will require longer-lived radionuclides to detect cerebral uptake at later tunes after injection to allow for complete clearance from the blood. Afternately, imaging using labeled AΒ itself may provide a means for noninvasive targeting of cerebral amyloid.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73674/1/j.1749-6632.1997.tb48475.x.pd

The Problem with Big Data: Operating on Smaller Datasets to Bridge the Implementation Gap

Big datasets have the potential to revolutionize public health. However, there is a mismatch between the political and scientific optimism surrounding big data and the public’s perception of its benefit. We suggest a systematic and concerted emphasis on developing models derived from smaller datasets to illustrate to the public how big data can produce tangible benefits in the long term. In order to highlight the immediate value of a small data approach, we produced a proof-of-concept model predicting hospital length of stay. The results demonstrate that existing small datasets can be used to create models that generate a reasonable prediction, facilitating health-care delivery. We propose that greater attention (and funding) needs to be directed toward the utilization of existing information resources in parallel with current efforts to create and exploit “big data.

An air-stable DPP-thieno-TTF copolymer for single-material solar cell devices and field effect transistors

Following an approach developed in our group to incorporate tetrathiafulvalene (TTF) units into conjugated polymeric systems, we have studied a low band gap polymer incorporating TTF as a donor component. This polymer is based on a fused thieno-TTF unit that enables the direct incorporation of the TTF unit into the polymer, and a second comonomer based on the diketopyrrolopyrrole (DPP) molecule. These units represent a donor–acceptor copolymer system, p(DPP-TTF), showing strong absorption in the UV–visible region of the spectrum. An optimized p(DPP-TTF) polymer organic field effect transistor and a single material organic solar cell device showed excellent performance with a hole mobility of up to 5.3 × 10–2 cm2/(V s) and a power conversion efficiency (PCE) of 0.3%, respectively. Bulk heterojunction organic photovoltaic devices of p(DPP-TTF) blended with phenyl-C71-butyric acid methyl ester (PC71BM) exhibited a PCE of 1.8%

Multiple value signals in dopaminergic midbrain and their role in avoidance contexts

The role of dopaminergic brain regions in avoidance behaviour is unclear. Active avoidance requires motivation, and the latter is linked to increased activity in dopaminergic regions. However, avoidance is also often tethered to the prospect of punishment, a state typically characterized by below baseline levels of dopaminergic function. Avoidance has been considered from the perspective of two-factor theories where the prospect of safety is considered to act as a surrogate for reward, leading to dopamine release and enhanced motivational drive. Using fMRI we investigated predictions from two-factor theory by separating the neural representation of a conventional net expected value, which is negative in the case of avoidance, from an adjusted expected value which factors in a possibility of punishment and is larger for both big rewards and big (predictably avoidable) punishments. We show that neural responses in ventral striatum and ventral tegmental area/substantial nigra (VTA/SN) covaried with net expected value. Activity in VTA/SN also covaried with an adjusted expected value, as did activity in anterior insula. Consistent with two-factor theory models, the findings indicate that VTA/SN and insula process an adjusted expected value during avoidance behaviour