Neutral genetic drift can aid functional protein evolution

BACKGROUND: Many of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve when selection begins to favor other, "promiscuous" functions that are incidental to a protein's biological role. If mutations that are neutral with respect to a protein's primary biological function cause substantial changes in promiscuous functions, these mutations could enable future functional evolution. RESULTS: Here we investigate this possibility experimentally by examining how cytochrome P450 enzymes that have evolved neutrally with respect to activity on a single substrate have changed in their abilities to catalyze reactions on five other substrates. We find that the enzymes have sometimes changed as much as four-fold in the promiscuous activities. The changes in promiscuous activities tend to increase with the number of mutations, and can be largely rationalized in terms of the chemical structures of the substrates. The activities on chemically similar substrates tend to change in a coordinated fashion, potentially providing a route for systematically predicting the change in one function based on the measurement of several others. CONCLUSIONS: Our work suggests that initially neutral genetic drift can lead to substantial changes in protein functions that are not currently under selection, in effect poising the proteins to more readily undergo functional evolution should selection "ask new questions" in the future

Highly Variable Extinction and Accretion in the Jet-driving Class I Type Young Star PTF 10nvg (V2492 Cyg, IRAS 20496+4354)

We report extensive new photometry and spectroscopy of the highly variable young stellar object PTF 10nvg including optical and near-infrared time series data as well as mid-infrared and millimeter data. Following the previously reported 2010 rise, during 2011 and 2012 the source underwent additional episodes of brightening and dimming events including prolonged faint states. The observed high-amplitude variations are largely consistent with extinction changes having a 220 day quasi-periodic signal. Spectral evolution includes not only changes in the spectral slope but correlated variation in the prominence of TiO/VO/CO bands and atomic line emission, as well as anticorrelated variation in forbidden line emission which, along with H_2, dominates optical and infrared spectra at faint epochs. Neutral and singly-ionized atomic species are likely formed in an accretion flow and/or impact while the origin of zero-velocity atomic LiI 6707 in emission is unknown. Forbidden lines, including several rare species, exhibit blueshifted emission profiles and likely arise from an outflow/jet. Several of these lines are also seen spatially offset from the continuum source position, presumably in a shocked region of an extended jet. CARMA maps resolve on larger scales a spatially extended outflow in mm-wavelength CO. We attribute the observed photometric and spectroscopic behavior in terms of occultation of the central star as well as the bright inner disk and the accretion/outflow zones that renders shocked gas in the inner part of the jet amenable to observation at the faint epochs. We discuss PTF 10nvg as a source exhibiting both accretion-driven (perhaps analogous to V1647 Ori) and extinction-driven (perhaps analogous to UX Ori or GM Cep) high-amplitude variability phenomena.Comment: accepted to AJ - in press (74 pages

Postprandial ghrelin suppression is exaggerated following major surgery; implications for nutritional recovery

Meeting patients' nutritional requirements and preventing malnutrition is a challenge following major surgical procedures. The role of ghrelin in nutritional recovery after non-gastrointestinal major surgery is unknown. We used coronary artery bypass grafting (CABG) as an example of anticipated good recovery post major surgery

GJ 3236: a new bright, very low-mass eclipsing binary system discovered by the MEarth observatory

We report the detection of eclipses in GJ 3236, a bright (I = 11.6) very low mass binary system with an orbital period of 0.77 days. Analysis of light- and radial velocity curves of the system yielded component masses of 0.38 +/- 0.02 and 0.28 +/- 0.02 Msol. The central values for the stellar radii are larger than the theoretical models predict for these masses, in agreement with the results for existing eclipsing binaries, although the present 5% observational uncertainties limit the significance of the larger radii to approximately 1 sigma. Degeneracies in the light curve models resulting from the unknown configuration of surface spots on the components of GJ 3236 currently dominate the uncertainties in the radii, and could be reduced by obtaining precise, multi-band photometry covering the full orbital period. The system appears to be tidally synchronized and shows signs of high activity levels as expected for such a short orbital period, evidenced by strong Halpha emission lines in the spectra of both components. These observations probe an important region of mass-radius parameter space around the predicted transition to fully-convective stellar interiors, where there are a limited number of precise measurements available in the literature.Comment: 14 pages, 5 figures, 10 tables, emulateapj format. Accepted for publication in Ap

A Study of the Diverse T Dwarf Population Revealed by WISE

We report the discovery of 87 new T dwarfs uncovered with the Wide-field Infrared Survey Explorer (WISE) and three brown dwarfs with extremely red near-infrared colors that exhibit characteristics of both L and T dwarfs. Two of the new T dwarfs are likely binaries with L7+/-1 primaries and mid-type T secondaries. In addition, our follow-up program has confirmed 10 previously identified T dwarfs and four photometrically-selected L and T dwarf candidates in the literature. This sample, along with the previous WISE discoveries, triples the number of known brown dwarfs with spectral types later than T5. Using the WISE All-Sky Source Catalog we present updated color-color and color-type diagrams for all the WISE-discovered T and Y dwarfs. Near-infrared spectra of the new discoveries are presented, along with spectral classifications. To accommodate later T dwarfs we have modified the integrated flux method of determining spectral indices to instead use the median flux. Furthermore, a newly defined J-narrow index differentiates the early-type Y dwarfs from late-type T dwarfs based on the J-band continuum slope. The K/J indices for this expanded sample show that 32% of late-type T dwarfs have suppressed K-band flux and are blue relative to the spectral standards, while only 11% are redder than the standards. Comparison of the Y/J and K/J index to models suggests diverse atmospheric conditions and supports the possible re-emergence of clouds after the L/T transition. We also discuss peculiar brown dwarfs and candidates that were found not to be substellar, including two Young Stellar Objects and two Active Galactic Nuclei. The coolest WISE-discovered brown dwarfs are the closest of their type and will remain the only sample of their kind for many years to come.Comment: Accepted to ApJS on 15 January 2013; 99 pages in preprint format, 30 figures, 12 table

Evidence for an FU Orionis-like Outburst from a Classical T Tauri Star

We present pre- and post-outburst observations of the new FU Orionis-like young stellar object PTF 10qpf (also known as LkHa 188-G4 and HBC 722). Prior to this outburst, LkHa 188-G4 was classified as a classical T Tauri star on the basis of its optical emission-line spectrum superposed on a K8-type photosphere, and its photometric variability. The mid-infrared spectral index of LkHa 188-G4 indicates a Class II-type object. LkHa 188-G4 exhibited a steady rise by ~1 mag over ~11 months starting in Aug. 2009, before a subsequent more abrupt rise of > 3 mag on a time scale of ~2 months. Observations taken during the eruption exhibit the defining characteristics of FU Orionis variables: (i) an increase in brightness by > 4 mag, (ii) a bright optical/near-infrared reflection nebula appeared, (iii) optical spectra are consistent with a G supergiant and dominated by absorption lines, the only exception being Halpha which is characterized by a P Cygni profile, (iv) near-infrared spectra resemble those of late K--M giants/supergiants with enhanced absorption seen in the molecular bands of CO and H_2O, and (v) outflow signatures in H and He are seen in the form of blueshifted absorption profiles. LkHa 188-G4 is the first member of the FU Orionis-like class with a well-sampled optical to mid-infrared spectral energy distribution in the pre-outburst phase. The association of the PTF 10qpf outburst with the previously identified classical T Tauri star LkHa 188-G4 (HBC 722) provides strong evidence that FU Orionis-like eruptions represent periods of enhanced disk accretion and outflow, likely triggered by instabilities in the disk. The early identification of PTF 10qpf as an FU Orionis-like variable will enable detailed photometric and spectroscopic observations during its post-outburst evolution for comparison with other known outbursting objects.Comment: 14 pages, 11 figures, ApJ accepte

Arterial versus venous lactate: a measure of sepsis in children.

This study assessed the agreement between arterial and venous blood lactate and pH levels in children with sepsis. This retrospective, three-year study involved 60 PICU patients, with data collected from electronic or paper patient records. The inclusion criteria comprised of children (≤17 years old) with sepsis and those who had a venous blood gas taken first with an arterial blood gas taken after within one hour. The lactate and pH values measured through each method were analysed. There is close agreement between venous and arterial lactate up to 2 mmol/L. As this value increases, this agreement becomes poor. The limits of agreement (LOA) are too large (±1.90 mmol/L) to allow venous and arterial lactate to be used interchangeably. The mean difference and LOA between both methods would be much smaller if derived using lactate values under 2.0 mmol/L. There is close agreement between arterial and venous pH (MD = -0.056, LOA ± 0.121). However, due to extreme variations in pH readings during sepsis, pH alone is an inadequate marker. CONCLUSION: A venous lactate ≤2 mmol/L can be used as a surrogate for arterial lactate during early management of sepsis in children. However, if the value exceeds 2 mmol/L, an arterial sample must confirm the venous result. What is known: • In children with septic shock, a blood gas is an important test to show the presence of acidosis and high lactic acid. Hyperlactataemia on admission is an early predictor of outcome and is associated with a greater mortality risk. • An arterial sample is the standard for lactate measurement, however getting a sample may be challenging in the emergency department or a general paediatric ward. Venous samples are quicker and easier to obtain. Adult studies generally advise caution in replacing venous lactate values for the arterial standard, whilst paediatric studies are limited in this area. What is new: • This is the first study assessing the agreement between arterial and peripheral venous lactate in children with sepsis, with a significant sample of patients. • This study shows that a venous sample with a lactate of ≤ 2 mmol/L can be used as a surrogate measurement for arterial lactate during early management of sepsis in children. However, if the venous lactate is above 2 mmol/L, an arterial sample must be taken to confirm the result

Mortality and Cardiovascular Disease among Older Live Kidney Donors

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation

The Impact of the COVID-19 Pandemic on College Student’s Stress and Physical Activity Levels

Background: The coronavirus disease 2019 (COVID-19) pandemic adversely disrupted university student educational experiences worldwide, with consequences that included increased stress levels and unhealthy sedentary behavior. Aim: This study aimed to quantify the degree of impact that COVID-19 had on the levels of physical activity and stress of university students by utilizing wearable fitness tracker data and standard stress survey instrument scores before and during the pandemic. Methods: We collected Fitbit heart rate and physical activity data, and the results of a modified Social Readjustment Rating Scale (SRRS) stress survey from 2,987 university students during the Fall 2019 (residential instruction; before COVID-19) and Fall 2020 (hybrid instruction; during COVID-19) semesters. Results: We found indicators of increased sedentary behavior during the pandemic. There was a significant decrease in both the levels of physical activity as measured by mean daily step count (↓636 steps/day; p = 1.04 · 10-9) and minutes spent in various heart rate zones (↓58 minutes/week; p = 2.20 · 10-16). We also found an increase in stressors during the pandemic, primarily from an increase in the number of students who experienced the “death of a close family member” (38.8%), with the number even higher for the population of students who opted to stay home and attend classes virtually (41.4%). Conclusions: This study quantifies the decrease in levels of physical activity and notes an increase in the number of students who experienced the death of a close family member, a known stressor, during the first year of the COVID-19 pandemic. These findings allow for more informed student-health-focused interventions related to the COVID-19 pandemic disruptions experienced by academic communities worldwide