“everything in one place”

Purpose: To describe older adults’ perspectives on a new patient education manual for the recovery process after hip fracture. Materials and methods: The Fracture Recovery for Seniors at Home (FReSH) Start manual is an evidence- based manual for older adults with fall-related hip fracture. The manual aims to support the transition from hospital to home by facilitating self- management of the recovery process. We enrolled 31 community-dwelling older adults with previous fall-related hip fracture and one family member. We collected data using a telephone-based questionnaire with eight five-point Likert items and four semi-structured open-ended questions to explore participants’ perceptions on the structure, content, and illustration of the manual. The questionnaire also asked participants to rate the overall utility (out of 10 points) and length of the manual. We used content analysis to describe main themes from responses to the open-ended interview questions. Results: Participants’ ratings for structure, content, and illustrations ranged from 4 to 5 (agree to highly agree), and the median usefulness rating was 9 (10th percentile: 7, 90th percentile: 10). Main themes from the content analysis included: ease of use and presentation; health literacy; illustration utility; health care team delivery; general impression, information support from hospital to home; emotional and decision-making support; and the novelty of the manual. Conclusion: The FReSH Start manual was perceived as comprehensive in content and acceptable for use with older adults post-fall- related hip fracture. Participants expressed a need for delivery and explanation of the manual by a health care team member

Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies

Cytoplasmic RNA granules serve key functions in the control of messenger RNA (mRNA) fate in eukaryotic cells. For instance, in yeast, severe stress induces mRNA relocalization to sites of degradation or storage called processing bodies (P-bodies). In this study, we show that the translation repression associated with glucose starvation causes the key translational mediators of mRNA recognition, eIF4E, eIF4G, and Pab1p, to resediment away from ribosomal fractions. These mediators then accumulate in P-bodies and in previously unrecognized cytoplasmic bodies, which we define as EGP-bodies. Our kinetic studies highlight the fundamental difference between EGP- and P-bodies and reflect the complex dynamics surrounding reconfiguration of the mRNA pool under stress conditions. An absence of key mRNA decay factors from EGP-bodies points toward an mRNA storage function for these bodies. Overall, this study highlights new potential control points in both the regulation of mRNA fate and the global control of translation initiation

A Neuroeconomics Approach to Inferring Utility Functions in Sensorimotor Control

Making choices is a fundamental aspect of human life. For over a century experimental economists have characterized the decisions people make based on the concept of a utility function. This function increases with increasing desirability of the outcome, and people are assumed to make decisions so as to maximize utility. When utility depends on several variables, indifference curves arise that represent outcomes with identical utility that are therefore equally desirable. Whereas in economics utility is studied in terms of goods and services, the sensorimotor system may also have utility functions defining the desirability of various outcomes. Here, we investigate the indifference curves when subjects experience forces of varying magnitude and duration. Using a two-alternative forced-choice paradigm, in which subjects chose between different magnitude–duration profiles, we inferred the indifference curves and the utility function. Such a utility function defines, for example, whether subjects prefer to lift a 4-kg weight for 30 s or a 1-kg weight for a minute. The measured utility function depends nonlinearly on the force magnitude and duration and was remarkably conserved across subjects. This suggests that the utility function, a central concept in economics, may be applicable to the study of sensorimotor control

Inception of a global atlas of sea levels since the Last Glacial Maximum

Determining the rates, mechanisms, and geographic variability of relative sea-level (RSL) change following the Last Glacial Maximum (LGM) provides insight into the sensitivity of ice sheets to climate change, the response of the solid Earth and gravity field to ice-mass redistribution, and constrains statistical and physical models used to project future sea-level rise. To do so in a scientifically robust way requires standardized datasets that enable broad spatial comparisons that minimize bias. As part of a larger goal to develop a unified, spatially-comprehensive post-LGM global RSL database, in this special issue we provide a standardized global synthesis of regional RSL data that resulted from the first ‘Geographic variability of HOLocene relative SEA level (HOLSEA)’ meetings in Mt Hood, Oregon (2016) and St Lucia, South Africa (2017). The HOLSEA meetings brought together sea-level researchers to agree upon a consistent protocol to standardize, interpret, and incorporate realistic uncertainties of RSL data. This special issue provides RSL data from ten geographical regions including new databases from Atlantic Europe and the Russian Arctic and revised/expanded databases from Atlantic Canada, the British Isles, the Netherlands, the western Mediterranean, the Adriatic, Israel, Peninsular Malaysia, Southeast Asia, and the Indian Ocean. In total, the database derived from this special issue includes 5634 (5290 validated) index (n = 3202) and limiting points (n = 2088) that span from ∼20,000 years ago to present. Progress in improving the standardization of sea-level databases has also been accompanied by advancements in statistical and analytical methods used to infer spatial patterns and rates of RSL change from geological data that have a spatially and temporally sparse distribution and geochronological and elevational uncertainties. This special issue marks the inception of a unified, spatially-comprehensive post-LGM global RSL database

Phonon drag thermopower and weak localization

Previous experimental work on a two-dimensional (2D) electron gas in a Si-on-sapphire device led to the conclusion that both conductivity and phonon drag thermopower $S^g$ are affected to the same relative extent by weak localization. The present paper presents further experimental and theoretical results on these transport coefficients for two very low mobility 2D electron gases in $\delta-$doped GaAs/Ga$_x$Al$_{1-x}$As quantum wells. The experiments were carried out in the temperature range 3-7K where phonon drag dominates the thermopower and, contrary to the previous work, the changes observed in the thermopower due to weak localization were found to be an order of magnitude less than those in the conductivity. A theoretical framework for phonon drag thermopower in 2D and 3D semiconductors is presented which accounts for this insensitivity of $S^g$ to weak localization. It also provides transparent physical explanations of many previous experimental and theoretical results.Comment: 19 page Revtex file, 3 Postscript figur

Constitutively-stressed yeast strains are high-yielding for recombinant Fps1:implications for the translational regulation of an aquaporin

Background: We previously selected four strains of Saccharomyces cerevisiae for their ability to produce the aquaporin Fps1 in sufficient yield for further study. Yields from the yeast strains spt3Δ, srb5Δ, gcn5Δ and yTHCBMS1 (supplemented with 0.5 μg/mL doxycycline) that had been transformed with an expression plasmid containing 249 base pairs of 5′ untranslated region (UTR) in addition to the primary FPS1 open reading frame (ORF) were 10–80 times higher than yields from wild-type cells expressing the same plasmid. One of the strains increased recombinant yields of the G protein-coupled receptor adenosine receptor 2a (A2aR) and soluble green fluorescent protein (GFP). The specific molecular mechanisms underpinning a high-yielding Fps1 phenotype remained incompletely described. Results: Polysome profiling experiments were used to analyze the translational state of spt3Δ, srb5Δ, gcn5Δ and yTHCBMS1 (supplemented with 0.5 μg/mL doxycycline); all but gcn5Δ were found to exhibit a clear block in translation initiation. Four additional strains with known initiation blocks (rpl31aΔ, rpl22aΔ, ssf1Δ and nop1Δ) also improved the yield of recombinant Fps1 compared to wild-type. Expression of the eukaryotic transcriptional activator GCN4 was increased in spt3Δ, srb5Δ, gcn5Δ and yTHCBMS1 (supplemented with 0.5 μg/mL doxycycline); these four strains also exhibited constitutive phosphorylation of the eukaryotic initiation factor, eIF2α. Both responses are indicative of a constitutively-stressed phenotype. Investigation of the 5′UTR of FPS1 in the expression construct revealed two untranslated ORFs (uORF1 and uORF2) upstream of the primary ORF. Deletion of either uORF1 or uORF1 and uORF2 further improved recombinant yields in our four strains; the highest yields of the uORF deletions were obtained from wild-type cells. Frame-shifting the stop codon of the native uORF (uORF2) so that it extended into the FPS1 ORF did not substantially alter Fps1 yields in spt3Δ or wild-type cells, suggesting that high-yielding strains are able to bypass 5′uORFs in the FPS1 gene via leaky scanning, which is a known stress-response mechanism. Yields of recombinant A2aR, GFP and horseradish peroxidase could be improved in one or more of the yeast strains suggesting that a stressed phenotype may also be important in high-yielding cell factories. Conclusions: Regulation of Fps1 levels in yeast by translational control may be functionally important; the presence of a native uORF (uORF2) may be required to maintain low levels of Fps1 under normal conditions, but higher levels as part of a stress response. Constitutively-stressed yeast strains may be useful high-yielding microbial cell factories for recombinant protein production

Ready ... Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival Time

What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the “go” signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a “countdown” condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in “no-go” conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals