Stereociliary Myosin-1c Receptors Are Sensitive to Calcium Chelation and Absent from Cadherin 23 Mutant Mice

The identities of some of the constituents of the hair-cell transduction apparatus have been elucidated only recently. The molecular motor myosin-1c (Myo1c) functions in adaptation of the hair-cell response to sustained mechanical stimuli and is therefore an integral part of the transduction complex. Recent data indicate that Myo1c interacts in vitro with two other molecules proposed to be important for transduction: cadherin 23 (Cdh23), a candidate for the stereociliary tip link, and phosphatidylinositol 4,5-bisphosphate (PIP2), which is abundant in the membranes of hair-cell stereocilia. It is not known, however, whether these interactions occur in hair cells. Using an in situ binding assay on saccular hair cells, we demonstrated previously that Myo1c interacts with molecules at stereociliary tips, the site of transduction, through sequences contained within its calmodulin (CaM)-binding neck domain, which can bind up to four CaM molecules. In the current study, we identify the second CaM-binding IQ domain as a region of Myo1c that mediates CaM-sensitive binding to stereociliary tips and to PIP2 immobilized on a solid support. Binding of Myo1c to stereociliary tips of cochlear and vestibular hair cells is disrupted by treatments that break tip links. In addition, Myo1c does not bind to stereocilia from mice whose hair cells lack Cdh23 protein despite the presence of PIP2 in the stereociliary membranes. Collectively, our data suggest that Myo1c and Cdh23 interact at the tips of hair-cell stereocilia and that this interaction is modulated by CaM

Effect of high intensity interval training on functional movement in older adults:A systematic review and meta-analysis

Abstract Background Preserving physiological functional capacity (PFC), the ability to perform the activities of daily life, and the ease with which they can be performed, in older adults, defined for this study as ≥ 50 years of age, is an important consideration for maintaining health and independence through the ageing process. Physical activity, and exercise training in particular, has been positively associated with improvement in PFC. In addition to improving aerobic and anaerobic capacity, promoting and preserving functional movement as a component of PFC is an important goal of physical activity, especially for older adults. High-intensity interval training (HIIT), an exercise protocol where repeated bouts of increased intensity are interspersed with active or passive recovery periods, has often been studied as an alternative to traditional moderate-intensity continuous training (MICT) exercise, where a continuous intensity is maintained throughout the exercise session. A large body of research has determined that both types of exercise programme are effective in improving measures of aerobic and anaerobic fitness in older adults. However, the effect of the two exercise modalities on functional movement has most often been a secondary outcome, with a range of observational techniques applied for measurement. Objectives The primary objective of this research is to systematically review and meta-analyse published studies of HIIT interventions that measured functional movement in older adults to conclude if HIIT is effective for improving functional movement. A secondary objective is to determine if there are significant differences between HIIT and MICT effect on functional movement. Methods A search strategy of terms locating studies of HIIT interventions, functional movement outcome measures, and older adult population samples was executed on seven digital databases. Randomized and pair-matched trials of > 2 weeks were considered for inclusion. Studies of participants with neurological impairment or studies using combined exercise modality were rejected. Standardized mean difference for functional movement outcome measures was calculated. A meta-analysis of the included studies and subgroups was performed along with study quality (risk of bias and publication bias) evaluation. Results A total of 18 studies were included in random effects model pooled analysis. Subgroup analysis of HIIT versus MICT on functional movement showed a trivial effect in favour of HIIT (ES 0.13, 95% CI [−0.06, 0.33] p = 0.18) and did not achieve statistical significance. However, HIIT showed a medium, statistically significant favourable effect on functional movement versus non-intervention control (ES = 0.60 95% CI [0.24, 0.95] p = 0.001). Further subgroups analysis using singular and multiple functional movement outcome measures showed similar results. Conclusion This meta-analysis indicates that HIIT interventions in older adults may be effective at promoting improvements in functional movement, though it is unclear whether HIIT is superior to MICT

User-centred improvements to energy efficiency products and renewable energy systems: research on household adoption and use

The development and rapid consumer adoption of energy efficiency products and renewable energy systems are key elements of the UK and the EU carbon reduction strategies to meet the challenge of climate change. Many such technologies are available for domestic use, but despite government incentives to meet carbon reduction targets consumer adoption has been slow. This Open University research with 111 in-depth interviews plus an on-line survey with nearly 400 responses, investigates consumer adoption, non-adoption and use of these technologies. Results show that it is important to research consumer use experiences, problems and requirements when designing and developing “green” technologies. With results tailored to each technology, this study shows that user-centred improvements are required to improve functionality, ergonomics, inter-connectedness with other systems and symbolic value, and to reduce cost and payback. User-centred research supports new product/system design and development to promote more rapid adoption and carbon-saving use of energy efficient and renewable technologies in homes

Diversity of supernovae Ia determined using equivalent widths of Si II 4000

Spectroscopic and photometric properties of low and high-z supernovae Ia (SNe Ia) have been analyzed in order to achieve a better understanding of their diversity and to identify possible SN Ia sub-types. We use wavelet transformed spectra in which one can easily measure spectral features. We investigate the \ion{Si}{II} 4000 equivalent width (EW_w\lbrace\ion{Si}{II}\rbrace). The ability and, especially, the ease in extending the method to SNe at high-$z$ is demonstrated. We applied the method to 110 SNe Ia and found correlations between EW_w\lbrace\ion{Si}{II}\rbrace and parameters related to the light-curve shape for 88 supernovae with available photometry. No evidence for evolution of EW_w\lbrace\ion{Si}{II}\rbrace with redshift is seen. Three sub-classes of SNe Ia were confirmed using an independent cluster analysis with only light-curve shape, colour, and EW_w\lbrace\ion{Si}{II}\rbrace. SNe from high-$z$ samples seem to follow a similar grouping to nearby objects. The EW_w\lbrace\ion{Si}{II}\rbrace value measured on a single spectrum may point towards SN Ia sub-classification, avoiding the need for expansion velocity gradient calculations.Comment: 12 pages, 5 figure

SALT: a Spectral Adaptive Light curve Template for Type Ia Supernovae

We present a new method to parameterize Type Ia Supernovae (SN Ia) multi-color light curves. The method was developed in order to analyze the large number of SN Ia multi-color light curves measured in current high-redshift projects. The technique is based on empirically modeling SN Ia luminosity variations as a function of phase, wavelength, a shape parameter, and a color parameter. The model is trained with a sample of well measured nearby SN Ia and then tested with an independent set of supernovae by building an optimal luminosity distance estimator combining the supernova rest-frame luminosity, shape parameter and color reconstructed with the model. The distances we measure using B- and V-band data show a dispersion around the Hubble line comparable or lower than obtained with other methods. With this model, we are able to measure distances using U- and B-band data with a dispersion around the Hubble line of 0.16 +- 0.05.Comment: Accepted in A&A, June 23, 2005 (printer friendly replacement version, includes language corrections

Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria.

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response

Effects of hippocampal damage on reward threshold and response rate during self-stimulation of the ventral tegmental area in the rat

The main purpose of this study was to explore the role of the hippocampus in motivated behavior. Rats with bilateral excitotoxic lesions of the hippocampus and controls were trained to lever press for electrical stimulation of the ventral tegmental area. Rate intensity functions were generated from an ascending and descending series of current intensities. Lesion-induced changes in sensitivity to reward were distinguished from enhancements in motor output by calculating reward thresholds and maximal response rates from the rate-intensity functions. Rats with hippocampal damage showed lower reward thresholds and higher maximal response rates than controls. These results provide further evidence of hippocampal modulation of the nucleus accumbens, suggesting that lesions of this structure enhance sensitivity to reward and increase motor output

Supernova light-curve fitters and Dark Energy

We show that when a procedure is made to remove the tension between a supernova Ia (SN Ia) data set and observations from BAO and CMB, there might be the case where the same SN Ia set built with two different light-curve fitters behaves as two separate and distinct supernova sets, and the tension found by some authors between supernova sets actually could be due to tension or inconsistency between fitters. We also show that the information of the fitter used in an SN Ia data set could be relevant to determine whether phantom type models are favored or not when such a set is combined with the BAO/CMB joint parameter.Comment: 8 pages, 7 figures and 2 tables. Improved version. Accepted in Phys. Lett.

Near-Infrared Properties of Type Ia Supernovae

The photometric properties of Type Ia supernovae (SNe Ia) in the near-infrared as garnered from observations made over the last 30 years are reviewed. During this period, light curves for more than 120 nearby SNe Ia have been published, revealing considerable homogeneity but also some fascinating differences. These data have confirmed that, for all but the fastest declining objects, SNe Ia are essentially perfect standard candles in the near-infrared, displaying only a slight dependence of peak luminosity on decline rate and color.Comment: Accepted for publication in PASA, 24 pages, 9 figures; corrected typo