A Strategy for the Selective Imaging of Glycans Using Caged Metabolic Precursors

Glycans can be imaged by metabolic labeling with azidosugars followed by chemical reaction with imaging probes; however, tissue-specific labeling is difficult to achieve. Here we describe a strategy for the use of a caged metabolic precursor that is activated for cellular metabolism by enzymatic cleavage. An N-azidoacetylmannosamine derivative caged with a peptide substrate for the prostate-specific antigen (PSA) protease was converted to cell-surface azido sialic acids in a PSA-dependent manner. The approach has applications in tissue-selective imaging of glycans for clinical and basic research purposes. © 2010 American Chemical Society

Toward the detection of permafrost using land-surface temperature mapping

Permafrost is degrading under current warming conditions, disrupting infrastructure, releasing carbon from soils, and altering seasonal water availability. Therefore, it is important to quantitatively map the change in the extent and depth of permafrost. We used satellite images of land-surface temperature to recognize and map the zero curtain, i.e., the isothermal period of ground temperature during seasonal freeze and thaw, as a precursor for delineating permafrost boundaries from remotely sensed thermal-infrared data. The phase transition of moisture in the ground allows the zero curtain to occur when near-surface soil moisture thaws or freezes, and also when ice-rich permafrost thaws or freezes. We propose that mapping the zero curtain is a precursor to mapping permafrost at shallow depths. We used ASTER and a MODIS-Aqua daily afternoon land-surface temperature (LST) timeseries to recognize the zero curtain at the 1-km scale as a "proof of concept. " Our regional mapping of the zero curtain over an area around the 7000 m high volcano Ojos del Salado in Chile suggests that the zero curtain can be mapped over arid regions of the world. It also indicates that surface heterogeneity, snow cover, and cloud cover can hinder the effectiveness of our approach. To be of practical use in many areas, it may be helpful to reduce the topographic and compositional heterogeneity in order to increase the LST accuracy. The necessary finer spatial resolution to reduce these problems is provided by ASTER (90 m).Fil: Batbaatar, Jigjidsurengiin. University of Washington; Estados UnidosFil: Gillespie , Alan R.. University of Washington; Estados UnidosFil: Sletten, Ronald S.. University of Washington; Estados UnidosFil: Mushkin , Amit. University of Washington; Estados UnidosFil: Amit, Rivka. Geological Survey Of Israel; IsraelFil: Trombotto, Dario Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Liu , Lu. University of Washington; Estados UnidosFil: Petrie, Gregg. University of Washington; Estados Unido

Associations between number of consecutive night shifts and impairment of neurobehavioral performance during a subsequent simulated night shift

Objective: This study aimed to investigate sleep and circadian phase in the relationships between neurobehavioral performance and the number of consecutive shifts worked. Methods: Thirty-four shift workers [20 men, mean age 31.8 (SD 10.9) years] worked 2–7 consecutive night shifts immediately prior to a laboratory-based, simulated night shift. For 7 days prior, participants worked their usual shift sequence, and sleep was assessed with logs and actigraphy. Participants completed a 10-minute auditory psychomotor vigilance task (PVT) at the start (~21:00 hours) and end (~07:00 hours) of the simulated night shift. Mean reaction times (RT), number of lapses and RT distribution was compared between those who worked 2–3 consecutive night shifts versus those who worked 4–7 shifts. Results: Following 4–7 shifts, night shift workers had significantly longer mean RT at the start and end of shift, compared to those who worked 2–3 shifts. The slowest and fastest 10% RT were significantly slower at the start, but not end, of shift among participants who worked 4–7 nights. Those working 4–7 nights also demonstrated a broader RT distribution at the start and end of shift and had significantly slower RT based on cumulative distribution analysis (5th, 25th, 50th, 75th percentiles at the start of shift; 75th percentile at the end of shift). No group differences in sleep parameters were found for 7 days and 24 hours prior to the simulated night shift. Conclusion: A greater number of consecutive night shifts has a negative impact on neurobehavioral performance, likely due to cognitive slowing.M Magee, TL Sletten, SA Ferguson, RR Grunstein, C Anderson, DJ Kennaway, SW Lockley, SMW Rajaratna

Chronotype and environmental light exposure in a student population

In humans and most other species, changes in the intensity and duration of light provide a critical set of signals for the synchronisation of the circadian system to the astronomical day. The timing of activity within the 24 h day defines an individual’s chronotype, i.e. morning, intermediate or evening type. The aim of this study was to investigate the associations between environmental light exposure, due to geographical location, on the chronotype of university students. Over 6 000 university students from cities in the Northern Hemisphere (Oxford, Munich and Groningen) and Southern Hemisphere (Perth, Melbourne and Auckland) completed the Munich ChronoType Questionnaire. In parallel, light measures (daily irradiance, timing of sunrise and sunset) were compiled from satellite or ground stations at each of these locations. Our data shows that later mid-sleep point on free days (corrected for oversleep on weekends MFSsc) is associated with (i) residing further from the equator, (ii) a later sunset, (iii) spending more time outside and (iv) waking from sleep significantly after sunrise. However, surprisingly, MSFscdid not correlate with daily light intensity at the different geographical locations. Although these findings appear to contradict earlier studies suggesting that in the wider population increased light exposure is associated with an earlier chronotype, our findings are derived exclusively from a student population aged between 17 and 26 years. We therefore suggest that the age and occupation of our population increase the likelihood that these individuals will experience relatively little light exposure in the morning whilst encountering more light exposure later in the day, when light has a delaying effect upon the circadian system

Spectroscopy of 26^{26}F

The structure of the weakly-bound $^{26}_{\;\;9}$F$_{17}$ odd-odd nucleus, produced from $^{27,28}$Na nuclei, has been investigated at GANIL by means of the in-beam $\gamma$-ray spectroscopy technique. A single $\gamma$-line is observed at 657(7) keV in $^{26}_{9}$F which has been ascribed to the decay of the excited J=$2^+$ state to the J=1$^+$ ground state. The possible presence of intruder negative parity states in $^{26}$F is also discussed.Comment: 3 pages, 1 figure, accepted for publication in Physical Review

Reactivity of Biarylazacyclooctynones in Copper-Free Click Chemistry

The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Here we performed a systematic analysis of the effects of strain and electronics on the reactivity of cyclooctynes with azides through both experimental measurements and computational studies using a density functional theory (DFT) distortion/interaction transition state model. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Drawing on these results, we analyzed the relationship between alkyne bond angles, which we determined using X-ray crystallography, and reactivity, quantified by experimental second-order rate constants, for a range of cyclooctynes. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry

Prevalence of circadian misalignment and its association with depressive symptoms in delayed sleep phase disorder

Study Objective: To examine the prevalence of circadian misalignment in clinically diagnosed delayed sleep phase disorder (DSPD) and to compare mood and daytime functioning in those with and without a circadian basis for the disorder. Methods: One hundred and eighty-two DSPD patients aged 16–64 years, engaged in regular employment or school, underwent sleep–wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime (DBT), or non-circadian DSPD, defined as DLMO occurring before DBT. Results: One hundred and three patients (57%) were classified as circadian DSPD and 79 (43%) as non-circadian DSPD. DLMO occurred 1.66 hours later in circadian DSPD compared to non-circadian DSPD (p < .001). Moderate-severe depressive symptoms (Beck Depression Inventory-II) were more prevalent in circadian DSPD (14.0%) than in non-circadian DSPD (3.8%; p < .05). Relative to non-circadian DSPD patients, circadian DSPD patients had 4.31 times increased odds of at least mild depressive symptoms (95% CI 1.75 to 10.64; p < .01). No group differences were found for daytime sleepiness or function, but DSPD symptoms were rated by clinicians to be more severe in those with circadian DSPD. Conclusions: Almost half of patients clinically diagnosed with DSPD did not show misalignment between the circadian pacemaker and the DBT, suggesting that the reported difficulties initiating sleep at the DBT are unlikely to be explained by the (mis)timing of the circadian rhythm of sleep propensity. Circadian misalignment in DSPD is associated with increased depressive symptoms and DSPD symptom severity.Jade M. Murray, Tracey L. Sletten, Michelle Magee, Christopher Gordon, Nicole Lovato ... David J. Kennaway ... et al

Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: a double-blind, randomised clinical trial

Background: Delayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT). Methods: This randomised, placebo-controlled, double-blind clinical trial was conducted in an Australian outpatient DSWPD population. Following 1-wk baseline, clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) were randomised to 4-wk treatment with 0.5 mg fast-release melatonin or placebo 1 h before DBT for at least 5 consecutive nights per week. All patients received behavioural sleep-wake scheduling, consisting of bedtime scheduled at DBT. The primary outcome was actigraphic sleep onset time. Secondary outcomes were sleep efficiency in the first third of time in bed (SE T1) on treatment nights, subjective sleep-related daytime impairment (Patient Reported Outcomes Measurement Information System [PROMIS]), PROMIS sleep disturbance, measures of daytime sleepiness, clinician-rated change in illness severity, and DLMO time. Findings: Between September 13, 2012 and September 1, 2014, 307 participants were registered; 116 were randomised to treatment (intention-to-treat n = 116; n = 62 males; mean age, 29.0 y). Relative to baseline and compared to placebo, sleep onset occurred 34 min earlier (95% confidence interval [CI] −60 to −8) in the melatonin group. SE T1 increased; PROMIS sleep-related impairment, PROMIS sleep disturbance, insomnia severity, and functional disability decreased; and a greater proportion of patients showed more than minimal clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%) (P < 0.05). The groups did not differ in the number of nights treatment was taken per protocol. Post-treatment DLMO assessed in a subset of patients (n = 43) was not significantly different between groups. Adverse events included light-headedness, daytime sleepiness, and decreased libido, although rates were similar between treatment groups. The clinical benefits or safety of melatonin with long-term treatment were not assessed, and it remains unknown whether the same treatment regime would benefit patients experiencing DSWPD sleep symptomology without a delay in the endogenous melatonin rhythm. Conclusions: In this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling.Tracey L. Sletten, Michelle Magee, Jade M. Murray, Christopher J. Gordon, Nicole Lovato, David J. Kennaway, Stella M. Gwini, Delwyn J. Bartlett, Steven W. Lockley, Leon C. Lack, Ronald R. Grunstein, Shantha M.W. Rajaratnam, for the Delayed Sleep on Melatonin (DelSoM) Study Grou