Triacylglyceride production and autophagous responses in Chlamydomonas reinhardtii depend on resource allocation and carbon source.
To improve the economic viability of microalgal biodiesel, it will be essential to optimize the productivity of fuel molecules such as triacylglyceride (TAG) within the microalgal cell. To understand some of the triggers required for the metabolic switch to TAG production, we studied the effect of the carbon supply (acetate or CO₂) in Chlamydomonas reinhardtii (wild type and the starchless sta6 mutant) grown under low N availability. As expected, initial rates of TAG production were much higher when acetate was present than under strictly photosynthetic conditions, particularly for the sta6 mutant, which cannot allocate resources to starch. However, in both strains, TAG production plateaued after a few days in mixotrophic cultures, whereas under autotrophic conditions, TAG levels continued to rise. Moreover, the reduced growth of the sta6 mutant meant that the greatest productivity (measured as mg TAG liter⁻¹ day⁻¹) was found in the wild type growing autotrophically. Wild-type cells responded to low N by autophagy, as shown by degradation of polar (membrane) lipids and loss of photosynthetic pigments, and this was less in cells supplied with acetate. In contrast, little or no autophagy was observed in sta6 mutant cells, regardless of the carbon supply. Instead, very high levels of free fatty acids were observed in the sta6 mutant, suggesting considerable alteration in metabolism. These measurements show the importance of carbon supply and strain selection for lipid productivity. Our findings will be of use for industrial cultivation, where it will be preferable to use fast-growing wild-type strains supplied with gaseous CO₂ under autotrophic conditions rather than require an exogenous supply of organic carbon.


A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces.
Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 μL per mOsm in the ventricle and by 0.835 μL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema.


The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH-like 2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) Biosynthesis Enzyme PqsBC.
Pseudomonas aeruginosa is a bacterial pathogen that causes life-threatening infections in immunocompromised patients. It produces a large armory of saturated and mono-unsaturated 2-alkyl-4(1H)-quinolones (AQs) and AQ N-oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β-ketoacyl-acyl-carrier protein synthase III (FabH)-like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2-heptyl-4(1H)-quinolone (HHQ), by condensing octanoyl-coenzyme A (CoA) with 2-aminobenzoylacetate (2-ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium-chain acyl-CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono-unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl-binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH-enzymes, for which such structural transitions have been postulated but have never been observed.


Reanalysis of "Raptorex kriegsteini": a juvenile tyrannosaurid dinosaur from Mongolia.
The carnivorous Tyrannosauridae are among the most iconic dinosaurs: typified by large body size, tiny forelimbs, and massive robust skulls with laterally thickened teeth. The recently described small-bodied tyrannosaurid Raptorex kreigsteini is exceptional as its discovery proposes that many of the distinctive anatomical traits of derived tyrannosaurids were acquired in the Early Cretaceous, before the evolution of large body size. This inference depends on two core interpretations: that the holotype (LH PV18) derives from the Lower Cretaceous of China, and that despite its small size, it is a subadult or young adult. Here we show that the published data is equivocal regarding stratigraphic position and that ontogenetic reanalysis shows there is no reason to conclude that LH PV18 has reached this level of maturity. The probable juvenile status of LH PV18 makes its use as a holotype unreliable, since diagnostic features of Raptorex may be symptomatic of its immature status, rather than its actual phylogenetic position. These findings are consistent with the original sale description of LH PV18 as a juvenile Tarbosaurus from the Upper Cretaceous of Mongolia. Consequently, we suggest that there is currently no evidence to support the conclusion that tyrannosaurid skeletal design first evolved in the Early Cretaceous at small body size.


Catabolism of coniferyl aldehyde, ferulic acid and p-coumaric acid by Saccharomyces cerevisiae yields less toxic products.
Lignocellulosic substrates and pulping process streams are of increasing relevance to biorefineries for second generation biofuels and biochemical production. They are known to be rich in sugars and inhibitors such as phenolic compounds, organic acids and furaldehydes. Phenolic compounds are a group of aromatic compounds known to be inhibitory to fermentative organisms. It is known that inhibition of Sacchromyces cerevisiae varies among phenolic compounds and the yeast is capable of in situ catabolic conversion and metabolism of some phenolic compounds. In an approach to engineer a S. cerevisiae strain with higher tolerance to phenolic inhibitors, we selectively investigated the metabolic conversion and physiological effects of coniferyl aldehyde, ferulic acid, and p-coumaric acid in Saccharomyces cerevisiae. Aerobic batch cultivations were separately performed with each of the three phenolic compounds. Conversion of each of the phenolic compounds was observed on time-based qualitative analysis of the culture broth to monitor various intermediate and final metabolites. Coniferyl aldehyde was rapidly converted within the first 24 h, while ferulic acid and p-coumaric acid were more slowly converted over a period of 72 h. The conversion of the three phenolic compounds was observed to involved several transient intermediates that were concurrently formed and converted to other phenolic products. Although there were several conversion products formed from coniferyl aldehyde, ferulic acid and p-coumaric acid, the conversion products profile from the three compounds were similar. On the physiology of Saccharomyces cerevisiae, the maximum specific growth rates of the yeast was not affected in the presence of coniferyl aldehyde or ferulic acid, but it was significantly reduced in the presence of p-coumaric acid. The biomass yields on glucose were reduced to 73 and 54 % of the control in the presence of coniferyl aldehyde and ferulic acid, respectively, biomass yield increased to 127 % of the control in the presence of p-coumaric acid. Coniferyl aldehyde, ferulic acid and p-coumaric acid and their conversion products were screened for inhibition, the conversion products were less inhibitory than coniferyl aldehyde, ferulic acid and p-coumaric acid, indicating that the conversion of the three compounds by Saccharomyces cerevisiae was also a detoxification process. We conclude that the conversion of coniferyl aldehyde, ferulic acid and p-coumaric acid into less inhibitory compounds is a form of stress response and a detoxification process. We hypothesize that all phenolic compounds are converted by Saccharomyces cerevisiae using the same metabolic process. We suggest that the enhancement of the ability of S. cerevisiae to convert toxic phenolic compounds into less inhibitory compounds is a potent route to developing a S. cerevisiae with superior tolerance to phenolic compounds.


Developmental toxicity evaluation of diethyl and dimethyl phthalate in rats.
Diethyl phthalate (DEP) and dimethyl phthalate (DMP), phthalic acid ester (PAE) plasticizers, were evaluated for developmental toxicity because of reports in the literature that some PAE were embryotoxic and teratogenic. A previous study (Singh et al., '72) suggested that an increased incidence of skeletal defects in rats might result from gestational exposure to DEP (0.6-1.9 g/kg) or DMP (0.4-1.3 g/kg), ip, on gestational days (gd) 5, 10, and 15. In the current study DEP (0, 0.25, 2.5, and 5%) or DMP (0, 0.25, 1, and 5%) in feed (approximately 0.2-4.0 g/kg/day) were supplied to timed-mated rats from gd 6 to 15. Treatment with 5% DMP resulted in increased relative maternal liver weight. Also, animals exhibited reduced body weight gain during treatment (5% DEP or DMP) and during gestation (5% DEP). Weight gain corrected for gravid uterine weight was also reduced in animals fed 5% DEP. However, high-dose treatment with either DEP or DMP resulted in changes in food and water consumption paralleling the body weight reductions, suggesting that apparent toxic effects on maternal body weight may reflect PAE/feed unpalatability. Treatment with 2.5% DEP resulted in only transient changes in body weight during early treatment. The only maternal effects at 0.25 or 1% DMP were minor changes in food and/or water consumption, and there were no effects at 0.25% DEP. Thus, the NOAELs for maternal toxicity were 1% DMP and 0.25% DEP. In contrast to the observed maternal toxicity, there was no effect of DEP or DMP treatment on any parameter of embryo/fetal development, except an increased incidence of supernumerary ribs (a variation) in the 5% DEP group. These results do not support the conclusion of other investigators that DEP and DMP are potent developmental toxicants. Rather, they suggest that the short-chain PAE are less developmentally toxic than PAE with more complex substitution groups, e.g., di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate, and butyl benzyl phthalate.


Neurodegenerative Diseases: Can Caffeine Be a Powerful Ally to Weaken Neuroinflammation?
In recent years, there has been considerable research showing that coffee consumption seems to be beneficial to human health, as it contains a mixture of different bioactive compounds such as chlorogenic acids, caffeic acid, alkaloids, diterpenes and polyphenols. Neurodegenerative diseases (NDs) are debilitating, and non-curable diseases associated with impaired central, peripheral and muscle nervous systems. Several studies demonstrate that neuroinflammation mediated by glial cells-such as microglia and astrocytes-is a critical factor contributing to neurodegeneration that causes the dysfunction of brain homeostasis, resulting in a progressive loss of structure, function, and number of neuronal cells. This happens over time and leads to brain damage and physical impairment. The most known chronic NDs are represented by Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). According to epidemiological studies, regular coffee consumption is associated with a lower risk of neurodegenerative diseases. In this review, we summarize the latest research about the potential effects of caffeine in neurodegenerative disorders prevention and discuss the role of controlled caffeine delivery systems in maintaining high plasma caffeine concentrations for an extended time.


Measuring Recovery in Elite Rugby Players: The Brief Assessment of Mood, Endocrine Changes, and Power.
There is demand in applied sport settings to measure recovery briefly and accurately. Research indicates mood disturbance as the strongest psychological predictor of mental and physical recovery. The Brief Assessment of Mood (BAM) is a shortened version of the Profile of Mood States that can be completed in less than 30 s. The purpose of this study was to examine the BAM as a quick measure of mood in relation to recovery status in elite rugby players alongside established physiological markers of recovery. Using elite rugby union players (N = 12), this study examined the utility of BAM as an indicator of mental and physical recovery in elite athletes by exploring pattern change in mood disturbance, energy index, power output, cortisol, and testosterone 36 hr before and 12 hr, 36 hr, and 60 hr after a competitive rugby match. Repeated-measures multivariate analysis of variance indicated significant changes in all variables across the 4 time points (p < .05, η(2) range = .20-.48), concurrent with previous study findings. Although visual inspection of the graphs indicated that the pattern of change for mood disturbance and energy index mapped changes in all physiological variables, only a low correlation was observed for power output (r = - .34). Although BAM scores changed significantly over time in accordance with the hypotheses, further testing is required to confirm the utility of the BAM as a measure of recovery. The results indicate that the BAM could be used as 1 indicator of recovery status alongside other measures.


The 2015 National Canadian Homeless Youth Survey: Mental Health and Addiction Findings.
This study was designed to provide a representative description of the mental health of youth accessing homelessness services in Canada. It is the most extensive survey in this area to date and is intended to inform the development of mental health and addiction service and policy for this marginalized population. This study reports mental health-related data from the 2015 "Leaving Home" national youth homelessness survey, which was administered through 57 agencies serving homeless youth in 42 communities across the country. This self-reported, point-in-time survey assessed a broad range of demographic information, pre-homelessness and homelessness variables, and mental health indicators. Survey data were obtained from 1103 youth accessing Canadian homelessness services in the Nunavut territory and all Canadian provinces except for Prince Edward Island. Forty-two per cent of participants reported 1 or more suicide attempts, 85.4% fell in a high range of psychological distress, and key indicators of risk included an earlier age of the first episode of homelessness, female gender, and identifying as a sexual and/or gender minority (lesbian, gay, bisexual, transgender, queer, and 2 spirit [LGBTQ2S]). This study provides clear and compelling evidence of a need for mental health support for these youth, particularly LGBTQ2S youth and female youth. The mental health concerns observed here, however, must be considered in the light of the tremendous adversity in all social determinants faced by these youth, with population-level interventions best leveraged in prevention and rapid response.


Brassinosteroid-mediated stress tolerance in Arabidopsis shows interactions with abscisic acid, ethylene and salicylic acid pathways.
Brassinosteroids (BRs) play crucial roles in plant development and also promote tolerance to a range of abiotic stresses. Although much has been learned about their roles in plant development, the mechanisms by which BRs control plant stress responses and regulate stress-responsive gene expression are not fully known. Since BR interacts with other plant hormones, it is likely that the stress tolerance conferring ability of BR lies in part in its interactions with other stress hormones. Using a collection of Arabidopsis mutants that are either deficient in or insensitive to abscisic acid (ABA), ethylene (ET), jasmonic acid (JA) and salicylic acid (SA), we studied the effects of 24-epibrassinloide (EBR) on basic thermotolerance and salt tolerance of these mutants. The positive impact of EBR on thermotolerance in proportion to wild type was evident in all mutants studied, with the exception of the SA-insensitive npr1-1 mutant. EBR could rescue the ET-insensitive ein2 mutant from its hypersensitivity to salt stress-induced inhibition of seed germination, but remained ineffective in increasing the survival of eto1-1 (ET-overproducer) and npr1-1 seedlings on salt. The positive effect of EBR was significantly greater in the ABA-deficient aba1-1 mutant as compared to wild type, indicating that ABA masks BR effects in plant stress responses. Treatment with EBR increased expression of various hormone marker genes in both wild type and mutant seedlings, although to different levels. These results together indicate that the redox-sensitive protein NPR1 (NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1), a master regulator of SA-mediated defense genes, is likely a critical component of EBR-mediated increase in thermotolerance and salt tolerance, but it is not required for EBR-mediated induction of PR-1 (PATHOGENESIS-RELATED1) gene expression; that BR exerts anti-stress effects independently as well as through interactions with other hormones; that ABA inhibits BR effects during stress; and that BR shares transcriptional targets with other hormones.


Role of T and NK cells and IL7/IL7r interactions during neonatal maturation of lymph nodes.
Lymph node (LN) development depends on prenatal interactions occurring between LN inducer and LN organizer cells. We have distinguished defects in LN formation due to failure in embryonic development (aly/aly) from defects in postnatal maturation (Il2rgamma(-/-)Rag2(-/-)). Both mutant strains form normal primordial LNs with differing fate. In aly/aly mice, the LN primordium dissipates irreversibly late in gestation; in contrast, Il2rgamma(-/-)Rag2(-/-) LN anlage persists for a week after birth but disperses subsequently, a process reversible by neonatal transfer of WT IL7r(+) TCR(+) T or natural killer (NK) cells, suggesting a role for IL7/IL7r interactions. Thus, we reveal a unique stage of postnatal LN development during which mature lymphocytes and IL7/IL7r interactions may play an important role.


Movement of axoplasmic organelles on actin filaments assembled on acrosomal processes: evidence for a barbed-end-directed organelle motor.
The directionality of the actin-dependent motors on squid axoplasmic organelles was determined using actin filaments assembled on the barbed ends of acrosomal processes. Acrosomal processes were isolated from Limulus polyphemus sperm and incubated in monomeric actin under conditions that promoted barbed end assembly only. Newly assembled actin was stabilized and stained with rhodamine-phalloidin and the presence of filaments at the barbed ends of the acrosomal processes was verified by fluorescence microscopy and negative contrast electron microscopy. Axoplasmic organelles that dissociated from extruded axoplasm were observed by video microscopy to move along the newly assembled actin filaments at an average velocity of 1.1 +/- 0.3 microns/second. All organelles moved in the direction away from the acrosomal fragment and towards the tip of the actin filaments. Therefore, the actin-dependent organelle motor on axoplasmic organelles is a barbed-end-directed motor like other myosins analyzed. These findings support the conclusions that axoplasmic organelles are driven by a myosin-like motor along actin filaments and that these filaments as well as microtubules function in fast axonal transport.


Predation as a determinant of minimum group size in baboons.
Predation risk places a pressure on animals to adopt mechanisms by which they reduce their individual risk of being preyed on. However, a consensus on methods of determining predation risk has yet to be reached. One of the most widespread ways in which animals respond to predation risk is by living in groups. Minimum permissible group size is the smallest group size that animals are able to live in, given the habitat-specific predation risk they face. We explore ways in which predation risk can be measured and analyse its effect on minimum observed group size in baboons. Using data on predator density, habitat composition and baboon body size, we investigate the impact of the components of predation risk on baboon group size, and derive an equation that best predicts minimum group size. Minimum group size in baboons is related to predator density and female body mass. Both of these elements can, in turn, be estimated from environmental variables. These findings present support for the argument that group living in primates is a response to predation risk and offer potentially new ways of investigating carnivore and primate ecology.


Quantitation of RNA decay in dried blood spots during 20 years of storage.
Diseases with an onset during childhood or adult life can have their origin during fetal life or at birth. Neonatal blood dried on filter paper (Guthrie cards) collected for screening purposes is routinely stored for decades. In addition to clinical use, these filters in combination with patient registers constitute an invaluable resource for epidemiological and pathophysiological research. Although RNA has been successfully recovered from such filters even after decades of storage, the potential decay of RNA over time has not previously been investigated using quantitative methods. Filter papers (n=5) with dried blood spots from the Swedish National PKU register, stored for 1, 5, 10, 15 or 20 years were randomly selected. RNA was isolated from each sample, quantitated by spectrophotometry and reverse transcribed following DNase I treatment. Amplifiable cDNA was subsequently detected by real-time PCR using primers specific for transcripts encoding beta-actin. Transcripts encoding beta-actin were detected in all 25 samples analyzed at a mean threshold cycle (Ct) of 25 (SD 1.9). A one-way ANOVA indicated no significant effect of storage time on Ct values. The lack of significant decay of RNA in dried blood filters stored for up to 20 years suggests that such filters are useful for studies of RNA determinants of diseases with an onset in childhood as well as adult life.


BROCCOLI: Software for fast fMRI analysis on many-core CPUs and GPUs.
Analysis of functional magnetic resonance imaging (fMRI) data is becoming ever more computationally demanding as temporal and spatial resolutions improve, and large, publicly available data sets proliferate. Moreover, methodological improvements in the neuroimaging pipeline, such as non-linear spatial normalization, non-parametric permutation tests and Bayesian Markov Chain Monte Carlo approaches, can dramatically increase the computational burden. Despite these challenges, there do not yet exist any fMRI software packages which leverage inexpensive and powerful graphics processing units (GPUs) to perform these analyses. Here, we therefore present BROCCOLI, a free software package written in OpenCL (Open Computing Language) that can be used for parallel analysis of fMRI data on a large variety of hardware configurations. BROCCOLI has, for example, been tested with an Intel CPU, an Nvidia GPU, and an AMD GPU. These tests show that parallel processing of fMRI data can lead to significantly faster analysis pipelines. This speedup can be achieved on relatively standard hardware, but further, dramatic speed improvements require only a modest investment in GPU hardware. BROCCOLI (running on a GPU) can perform non-linear spatial normalization to a 1 mm(3) brain template in 4-6 s, and run a second level permutation test with 10,000 permutations in about a minute. These non-parametric tests are generally more robust than their parametric counterparts, and can also enable more sophisticated analyses by estimating complicated null distributions. Additionally, BROCCOLI includes support for Bayesian first-level fMRI analysis using a Gibbs sampler. The new software is freely available under GNU GPL3 and can be downloaded from github (https://github.com/wanderine/BROCCOLI/).


Robust estimation of peptide abundance ratios and rigorous scoring of their variability and bias in quantitative shotgun proteomics.
The abundance ratio between the light and heavy isotopologues of an isotopically labeled peptide can be estimated from their selected ion chromatograms. However, quantitative shotgun proteomics measurements yield selected ion chromatograms at highly variable signal-to-noise ratios for tens of thousands of peptides. This challenge calls for algorithms that not only robustly estimate the abundance ratios of different peptides but also rigorously score each abundance ratio for the expected estimation bias and variability. Scoring of the abundance ratios, much like scoring of sequence assignment for tandem mass spectra by peptide identification algorithms, enables filtering of unreliable peptide quantification and use of formal statistical inference in the subsequent protein abundance ratio estimation. In this study, a parallel paired covariance algorithm is used for robust peak detection in selected ion chromatograms. A peak profile is generated for each peptide, which is a scatterplot of ion intensities measured for the two isotopologues within their chromatographic peaks. Principal component analysis of the peak profile is proposed to estimate the peptide abundance ratio and to score the estimation with the signal-to-noise ratio of the peak profile (profile signal-to-noise ratio). We demonstrate that the profile signal-to-noise ratio is inversely correlated with the variability and bias of peptide abundance ratio estimation.


Influence on spectral energy distribution of emotional expression.
The aim of this study was to determine the influence of emotional expression in spectral energy distribution in professional theater actors. The study design is a quasi-experimental study. Thirty-seven actors, native Spanish speakers, were included. All subjects had at least 3 years of professional experience as a theater actor and no history of vocal pathology for the last 5 years. Participants were recorded during a read-aloud task of a 230-word passage, expressing six different emotions (happiness, sadness, fear, anger, tenderness, and eroticism) and without emotion (neutral state). Acoustical analysis with long-term average spectrum included three variables: the energy level difference between the F(1) and fundamental frequency (F(0)) regions, ratio between 1-5kHz and 5-8kHz, and alpha ratio. All the different emotions differ significantly from the neutral state for alpha ratio and 1-5/5-8kHz ratio. Only significant differences between "joy," "anger," and "eroticism" were found for L1-L0 ratio. Statistically significant differences between genders for the three acoustical variables were also found. The expression of emotion impacts the spectral energy distribution. On the one hand emotional states characterized by a breathy voice quality such as tenderness, sadness, and eroticism present a low harmonic energy above 1kHz, high glottal noise energy, and more energy on F(0) than overtones. On the other hand, emotional states such as joy, anger, and fear are characterized by high harmonic energy greater than 1kHz (less steep spectral slope declination), low glottal noise energy, and more energy on the F(1) than F(0) region.


Traffic-Related Air Pollution and Carotid Plaque Burden in a Canadian City With Low-Level Ambient Pollution.
Background The association between fine particulate matter and cardiovascular disease has been convincingly demonstrated. The role of traffic-related air pollutants is less clear. To better understand the role of traffic-related air pollutants in cardiovascular disease development, we examined associations between NO2, carotid atherosclerotic plaque, and cardiometabolic disorders associated with cardiovascular disease. Methods and Results Cross-sectional analyses were conducted among 2227 patients (62.9±13.8 years; 49.5% women) from the Stroke Prevention and Atherosclerosis Research Centre (SPARC) in London, Ontario, Canada. Total carotid plaque area measured by ultrasound, cardiometabolic disorders, and residential locations were provided by SPARC medical records. Long-term outdoor residential NO2 concentrations were generated by a land use regression model. Associations between NO2, total carotid plaque area, and cardiometabolic disorders were examined using multiple regression models adjusted for age, sex, smoking, and socioeconomic status. Mean NO2 was 5.4±1.6 ppb in London, Ontario. NO2 was associated with a significant increase in plaque (3.4 mm2 total carotid plaque area per 1 ppb NO2), exhibiting a linear dose-response. NO2 was also positively associated with triglycerides, total cholesterol, and the ratio of low- to high-density lipoprotein cholesterol (P<0.05). Diabetes mellitus mediated the relationship between NO2 and total carotid plaque area (P<0.05). Conclusions Our results demonstrate that even low levels of traffic-related air pollutants are linked to atherosclerotic plaque burden, an association that may be partially attributable to pollution-induced diabetes mellitus. Our findings suggest that reducing ambient concentrations in cities with NO2 below current standards would result in additional health benefits. Given the billions of people exposed to traffic emissions, our study supports the global public health significance of reducing air pollution.


The role of unbound oligomers in the nucleation and growth of electrodeposited polypyrrole and method for preparing high strength, high conductivity films.
Polypyrrole is a material with immensely useful properties suitable for a wide range of electrochemical applications, but its development has been hindered by cumbersome manufacturing processes. Here we show that a simple modification to the standard electrochemical polymerization method produces polypyrrole films of equivalently high conductivity and superior mechanical properties in one-tenth of the polymerization time. Preparing the film as a series of electrodeposited layers with thorough solvent washing between layering was found to produce excellent quality films even when layer deposition was accelerated by high current. The washing step between the sequentially polymerized layers altered the deposition mechanism, eliminating the typical dendritic growth and generating nonporous deposits. Solvent washing was shown to reduce the concentration of oligomeric species in the near-electrode region and hinder the three-dimensional growth mechanism that occurs by deposition of secondary particles from solution. As artificial muscles, the high density sequentially polymerized films produced the highest mechanical work output yet reported for polypyrrole actuators.


Functional equivalence of Escherichia coli sigma E and Pseudomonas aeruginosa AlgU: E. coli rpoE restores mucoidy and reduces sensitivity to reactive oxygen intermediates in algU mutants of P. aeruginosa.
Mucoid colony morphology is the result of the overproduction of the exopolysaccharide alginate and is considered to be a major pathogenic determinant expressed by Pseudomonas aeruginosa during chronic respiratory infections in cystic fibrosis. Conversion to mucoidy can be caused by mutations in the second or third gene of the stress-responsive system algU mucA mucB. AlgU is 66% identical to the alternative sigma factor RpoE (sigma E) from Escherichia coli and Salmonella typhimurium and directs transcription of several critical alginate biosynthetic and regulatory genes. AlgU is also required for the full resistance of P. aeruginosa to reactive oxygen intermediates and heat killing. In this work, we report that E. coli sigma E can complement phenotypic defects of algU inactivation in P. aeruginosa: (i) the rpoE gene from E. coli complemented an algU null mutant of P. aeruginosa to mucoidy; (ii) the presence of the E. coli rpoE gene in P. aeruginosa induced alginate production in the standard genetic nonmucoid strain PAO1; (iii) the plasmid-borne E. coli rpoE gene induced transcription of algD, a critical algU-dependent alginate biosynthetic gene; and (iv) when present in algU::Tcr mutants, E. coli rpoE partially restored resistance to paraquat, a redox cycling compound that increases intracellular levels of superoxide radicals. A new gene, mclA, encoding a polypeptide with an apparent molecular mass of 27.7 kDa was identified immediately downstream of rpoE in E. coli. The predicted product of this gene is 28% identical (72% similar) to MucA, a negative regulator of AlgU activity in P. aeruginosa. The results reported in this study demonstrate that RpoE and AlgU are functionally interchangeable in P. aeruginosa and suggest that elements showing sequence similarity to those known to regulate AlgU activity in P. aeruginosa are also present in other bacteria.


Theta rhythmicity governs human behavior and hippocampal signals during memory-dependent tasks.
Memory formation and reinstatement are thought to lock to the hippocampal theta rhythm, predicting that encoding and retrieval processes appear rhythmic themselves. Here, we show that rhythmicity can be observed in behavioral responses from memory tasks, where participants indicate, using button presses, the timing of encoding and recall of cue-object associative memories. We find no evidence for rhythmicity in button presses for visual tasks using the same stimuli, or for questions about already retrieved objects. The oscillations for correctly remembered trials center in the slow theta frequency range (1-5 Hz). Using intracranial EEG recordings, we show that the memory task induces temporally extended phase consistency in hippocampal local field potentials at slow theta frequencies, but significantly more for remembered than forgotten trials, providing a potential mechanistic underpinning for the theta oscillations found in behavioral responses.


Aurora-A and p16 polymorphisms contribute to an earlier age at diagnosis of pancreatic cancer in Caucasians.
Aurora-A and p16 play a major role in cell cycle checkpoint regulation. Both of them are important in the maintenance of centrosome duplication. Therefore, we hypothesized that polymorphisms in the two genes may interact or work together to influence the finely tuned mechanisms of cell cycle regulation that these proteins regulate. The purpose of this study was to investigate the association of the Aurora-A (T91A), and p16 (C540G and C580T) polymorphisms with age at diagnosis of pancreatic cancer. We genotyped 148 Caucasian patients with a diagnosis of pancreatic cancer for the Aurora-A and p16 polymorphisms using pyrosequencing. We tested the association between age at diagnosis and the Aurora-A and p16 genotypes by comparing Kaplan-Meier curves, evaluating the homogeneity of the curves using the log-rank test. We used Cox proportional hazard regression analysis to estimate the association between time to diagnosis and genotype, adjusting for gender. Patients with the Aurora-A polymorphic genotypes had a median age at diagnosis with pancreatic cancer that was 2.8 years earlier than those with the wild-type genotype [log-rank, P=0.015; hazard ratio (HR), 1.55; 95% confidence intervals (95% CI), 1.09-2.20]. There was no significant association between the p16 genotypes and age at diagnosis. However, the Aurora-A and p16 C580T polymorphisms combined had a synergistic effect on age-associated risk for early diagnosis of pancreatic cancer. Compared with patients with wild-type genotypes for both genes, the median age at diagnosis for patients with one or two polymorphic alleles for both genes was 12.6 years earlier (log-rank, P=0.0002; HR, 3.88; 95% CI, 1.94-7.76). No significant associations between the polymorphisms and the cancer metastatic status or survival after diagnosis were found. Our findings suggest that the Aurora-A polymorphism contributes to a significantly earlier age at diagnosis of pancreatic cancer, and that Aurora-A and p16 C580T polymorphisms synergistically contribute to an earlier age at diagnosis of pancreatic cancer.


Synaptic plasticity and memory: an evaluation of the hypothesis.
Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed." We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.


Socioeconomic position and early adolescent smoking development: evidence from the British Youth Panel Survey (1994-2008).
Smoking usually develops in adolescence and is patterned by socioeconomic position (SEP). We examined whether early adolescent smoking development and associations with SEP have changed over time in a population with well-developed tobacco control policies. We additionally investigated the relative importance of socioeconomic inequalities at different stages of smoking development. An annual UK rotating panel survey including data from 5122 adolescents (51% male) aged 11-15 years between 1994 and 2008. Rates of smoking initiation, progression to occasional smoking (experimentation), progression to daily smoking (escalation), and quitting were examined using discrete-time event history analysis. Initiation, experimentation and escalation rates declined over the study period while quitting rates increased. Decreases in initiation were concentrated among older adolescents and decreases in escalation among those who spent a year or two as occasional smokers. Socioeconomic disadvantage was associated with higher rates of initiation and escalation, with similar findings across SEP measures. Inequalities in initiation were stronger at younger ages. There was less evidence of associations between SEP and quitting or experimentation. Inequalities in escalation remained constant over time, while inequalities in initiation widened before narrowing. Further modelling suggested that differential initiation rates contributed more to inequalities in daily smoking at age 15 than did differential escalation. Increasing tobacco control in the UK is associated with reduced uptake and more quitting in early adolescence, but socioeconomic inequalities remain. Interventions should focus on reducing inequalities in initiation among early adolescents.


Pupillometric evidence for the decoupling of attention from perceptual input during offline thought.
Accumulating evidence suggests that the brain can efficiently process both external and internal information. The processing of internal information is a distinct "offline" cognitive mode that requires not only spontaneously generated mental activity; it has also been hypothesized to require a decoupling of attention from perception in order to separate competing streams of internal and external information. This process of decoupling is potentially adaptive because it could prevent unimportant external events from disrupting an internal train of thought. Here, we use measurements of pupil diameter (PD) to provide concrete evidence for the role of decoupling during spontaneous cognitive activity. First, during periods conducive to offline thought but not during periods of task focus, PD exhibited spontaneous activity decoupled from task events. Second, periods requiring external task focus were characterized by large task evoked changes in PD; in contrast, encoding failures were preceded by episodes of high spontaneous baseline PD activity. Finally, high spontaneous PD activity also occurred prior to only the slowest 20% of correct responses, suggesting high baseline PD indexes a distinct mode of cognitive functioning. Together, these data are consistent with the decoupling hypothesis, which suggests that the capacity for spontaneous cognitive activity depends upon minimizing disruptions from the external world.


Incidence, Risk Factors, and Effect on Survival of Immune-related Adverse Events in Patients With Non-Small-cell Lung Cancer.
The risk factors for immune-related adverse events (irAEs) remain undefined. Recently, a correlation between irAEs and clinical benefit was suggested. We examined the risk factors for irAEs and their effect on survival in patients with non-small-cell lung cancer (NSCLC) who had received immunotherapy. We performed a retrospective review of patients with NSCLC treated with single-agent immunotherapy at our institution. irAEs were determined by treating physician diagnosis. A landmark analysis was performed at 3 months using log-rank tests and the Bonferroni method. irAEs occurred in 27 of 91 patients (30%). The median overall survival (OS) for patients with irAEs was longer than that for patients without (24.3 vs. 5.3 months; hazard ratio, 2.75; 95% confidence interval, 1.54-4.92; P < .001). However, a landmark analysis of patients after 3 months of treatment revealed no difference in OS between patients with and without irAEs. No increased risk of pneumonitis was seen in patients with previous thoracic radiotherapy, although these patients had shorter survival (4.2 vs. 9.7 months; P = .004). Radiotherapy after the initiation of immunotherapy (n = 15) did not increase the risk of irAEs or pneumonitis; however, these patients had improved OS (17.3 vs. 6.0 months; P = .016). The development of irAEs did not significantly correlate with survival when controlling for the duration of therapy in a landmark analysis. We found no increased risk of pneumonitis or irAEs in patients who had received radiotherapy. Radiotherapy before immunotherapy was associated with shorter survival, and radiotherapy after immunotherapy was associated with improved survival.


Estimating heritabilities and genetic correlations: comparing the 'animal model' with parent-offspring regression using data from a natural population.
Quantitative genetic parameters are nowadays more frequently estimated with restricted maximum likelihood using the 'animal model' than with traditional methods such as parent-offspring regressions. These methods have however rarely been evaluated using equivalent data sets. We compare heritabilities and genetic correlations from animal model and parent-offspring analyses, respectively, using data on eight morphological traits in the great reed warbler (Acrocephalus arundinaceus). Animal models were run using either mean trait values or individual repeated measurements to be able to separate between effects of including more extended pedigree information and effects of replicated sampling from the same individuals. We show that the inclusion of more pedigree information by the use of mean traits animal models had limited effect on the standard error and magnitude of heritabilities. In contrast, the use of repeated measures animal model generally had a positive effect on the sampling accuracy and resulted in lower heritabilities; the latter due to lower additive variance and higher phenotypic variance. For most trait combinations, both animal model methods gave genetic correlations that were lower than the parent-offspring estimates, whereas the standard errors were lower only for the mean traits animal model. We conclude that differences in heritabilities between the animal model and parent-offspring regressions were mostly due to the inclusion of individual replicates to the animal model rather than the inclusion of more extended pedigree information. Genetic correlations were, on the other hand, primarily affected by the inclusion of more pedigree information. This study is to our knowledge the most comprehensive empirical evaluation of the performance of the animal model in relation to parent-offspring regressions in a wild population. Our conclusions should be valuable for reconciliation of data obtained in earlier studies as well as for future meta-analyses utilizing estimates from both traditional methods and the animal model.


Varying dependency of periplasmic peptidylprolyl cis-trans isomerases in promoting Yersinia pseudotuberculosis stress tolerance and pathogenicity.
Periplasmic PPIases (peptidylprolyl cis-trans isomerases) catalyse the cis-trans isomerization of peptidyl-prolyl bonds, which is a rate-limiting step during protein folding. We demonstrate that the surA, ppiA, ppiD, fkpA and fklB alleles each encode a periplasmic PPIase in the bacterial pathogen Yersinia pseudotuberculosis. Of these, four were purified to homogeneity. Purified SurA, FkpA and FklB, but not PpiD, displayed detectable PPIase activity in vitro. Significantly, only Y. pseudotuberculosis lacking surA caused drastic alterations to the outer membrane protein profile and FA (fatty acid) composition. They also exhibited aberrant cellular morphology, leaking LPS (lipopolysaccharide) into the extracellular environment. The SurA PPIase is therefore most critical for maintaining Y. pseudotuberculosis envelope integrity during routine culturing. On the other hand, bacteria lacking either surA or all of the genes ppiA, ppiD, fkpA and fklB were sensitive to hydrogen peroxide and were attenuated in mice infections. Thus Y. pseudotuberculosis exhibits both SurA-dependent and -independent requirements for periplasmic PPIase activity to ensure in vivo survival and a full virulence effect in a mammalian host.


Identification of mitochondrial markers for genetic traceability of European wild boars and Iberian and Duroc pigs.
Iberian pigs and wild boars are the source of highly priced meat and dry-cured products. Iberian maternal origin is mandatory for labeled Iberian products, making necessary the authentication of their maternal breed origin. Discrimination between wild and domestic pig maternal origin may be useful to distinguish labeled wild boar meat obtained from hunting or farming. In order to detect useful polymorphisms to trace Iberian, Duroc and wild boar maternal lineages, we herein investigated the complete porcine mitochondrial DNA (mtDNA) using three complementary approaches. Near-complete mtDNA sequences (16989 bp), excluding the minisatellite present in the displacement loop region (D-loop), were successfully determined in six Iberian pigs, two Duroc and six European wild boars. To complete the mtDNA analysis, the D-loop minisatellite region was also analyzed in the same set of samples by amplification and capillary electrophoresis detection. Finally, the frequencies of Asian and European Cytochrome B (Cyt B) haplotypes were estimated in Iberian (n = 96) and Duroc (n = 125) breeds. Comparison of near-complete mtDNA sequences revealed a total of 57 substitutions and two Indels. Out of them, 32 polymorphisms were potential Iberian markers, 10 potential Duroc markers and 16 potential wild boar markers. Fourteen potential markers (five Iberian and nine Duroc), were selected to be genotyped in 96 Iberian and 91 Duroc samples. Five wild boar potential markers were selected and tested in samples of wild boars (73) and domestic pigs including: 96 Iberian, 16 Duroc, 16 Large White and 16 Landrace. Genotyping results showed three linked markers (m.7998C>T, m.9111T>C, m.14719A>G) absent in Duroc and present in Iberian pigs with a frequency 0.72. Six markers (m.8158C>T, m.8297T>C, m.9230G>A, m.11859A>G, m.13955T>C, m.16933T>C), three of them linked, were absent in Iberian pigs and present in Duroc with a joint frequency of almost 0.50. Finally three linked markers (m.7188G>A, m.9224T>C, m.15823A>G) were solely detected in wild boars with a frequency 0.22. The D-loop minisatellite results showed overlapping ranges of fragment sizes and suggested heteroplasmy, a result that nullify the use of this region for the development of breed diagnostic markers. The Cyt B haplotype results showed the presence of European haplotypes in Iberian while one of the Asian haplotypes was detected in Duroc with a frequency 0.22, linked to the Duroc marker m.9230G>A. Our results are valuable to resolve the problems of Iberian and wild boar maternal origin determination but additional markers are required to achieve totally useful genetic tests.


Adenosine diphosphate-degrading activity in placenta.
1. The degradation of ADP by the placenta and umbilical artery was investigated. 2. Supernatants from incubations of finely chopped placental and umbilical arterial tissue were incubated with [14C]ADP for various durations from 0 to 30 min. 3. Products of ADP degradation were separated by thin-layer chromatography and radioactivity incorporated into each product was measured. 4. Placental supernatants induced a more rapid degradation of ADP than the umbilical artery supernatants. The main product of ADP degradation by placental supernatants at 30 min was adenosine, whereas that of umbilical artery was AMP. 5. This conversion by placenta of ADP, a potent platelet aggregator and vasoconstrictor, into adenosine, a potent platelet anti-aggregator and vasodilator, may be important in the maintenance of perfusion of the foetoplacental unit.


Chato, a KRAB zinc-finger protein, regulates convergent extension in the mouse embryo.
In Xenopus and zebrafish embryos, elongation of the anterior-posterior body axis depends on convergent extension, a process that involves polarized cell movements and is regulated by non-canonical Wnt signaling. The mechanisms that control axis elongation of the mouse embryo are much less well understood. Here, we characterize the ENU-induced mouse mutation chato, which causes arrest at midgestation and defects characteristic of convergent extension mutants, including a shortened body axis, mediolaterally extended somites and an open neural tube. The chato mutation disrupts Zfp568, a Krüppel-associated box (KRAB) domain zinc-finger protein. Morphometric analysis revealed that the definitive endoderm of mouse wild-type embryos undergoes cell rearrangements that lead to convergent extension during early somite stages, and that these cell rearrangements fail in chato embryos. Although non-canonical Wnt signaling is important for convergent extension in the mouse notochord and neural plate, the results indicate that chato regulates body axis elongation in all embryonic tissues through a process independent of non-canonical Wnt signaling.


Social Mindfulness and Psychosis: Neural Response to Socially Mindful Behavior in First-Episode Psychosis and Patients at Clinical High-Risk.
Background: Psychosis is characterized by problems in social functioning and trust, the assumed glue to positive social relations. But what helps building trust? A prime candidate could be social mindfulness: the ability and willingness to see and consider another person's needs and wishes during social decision making. We investigated whether first-episode psychosis patients (FEP) and patients at clinical high-risk (CHR) show reduced social mindfulness, and examined the underlying neural mechanisms. Methods: Twenty FEP, 17 CHR and 46 healthy controls, aged 16-31, performed the social mindfulness task (SoMi) during fMRI scanning, spontaneously and after the instruction "to keep the other's best interest in mind." As first of two people, participants had to choose one out of four products, of which three were identical and one was unique, differing in a single aspect (e.g., color). Results: FEP tended to choose the unique item (unmindful choice) more often than controls. After instruction, all groups significantly increased the number of mindful choices compared to the spontaneous condition. FEP showed reduced activation of the caudate and medial prefrontal cortex (mPFC) during mindful, and of the anterior cingulate cortex (ACC), mPFC, and left dorsolateral prefrontal cortex (dlPFC) during unmindful decisions. CHR showed reduced activation of the ACC compared to controls. Discussion: FEP showed a trend toward more unmindful choices. A similar increase of mindful choices after instruction indicated the ability for social mindfulness when prompted. Results suggested reduced sensitivity to the rewarding aspects of social mindfulness in FEP, and reduced consideration for the other player. FEP (and CHR to a lesser extent) might perceive unmindful choices as less incongruent with the automatic mindful responses than controls. Reduced socially mindful behavior in FEP may hinder the building of trust and cooperative interactions.


Dynamic motion analysis of fetuses with central nervous system disorders by cine magnetic resonance imaging using fast imaging employing steady-state acquisition and parallel imaging: a preliminary result.
The authors present a novel cine magnetic resonance (MR) imaging, two-dimensional (2D) fast imaging employing steady-state acquisition (FIESTA) technique with parallel imaging. It achieves temporal resolution at less than half a second as well as high spatial resolution cine imaging free of motion artifacts for evaluating the dynamic motion of fetuses in utero. The information obtained is used to predict postnatal outcome. Twenty-five fetuses with anomalies were studied. Ultrasonography demonstrated severe abnormalities in five of the fetuses; the other 20 fetuses constituted a control group. The cine fetal MR imaging demonstrated fetal head, neck, trunk, extremity, and finger as well as swallowing motions. Imaging findings were evaluated and compared in fetuses with major central nervous system (CNS) anomalies in five cases and minor CNS, non-CNS, or no anomalies in 20 cases. Normal motility was observed in the latter group. For fetuses in the former group, those with abnormal motility failed to survive after delivery, whereas those with normal motility survived with functioning preserved. The power deposition of radiofrequency, presented as specific absorption rate (SAR), was calculated. The SAR of FIESTA was approximately 13 times lower than that of conventional MR imaging of fetuses obtained using single-shot fast spin echo sequences. The following conclusions are drawn: 1) Fetal motion is no longer a limitation for prenatal imaging after the implementation of parallel imaging with 2D FIESTA, 2) Cine MR imaging illustrates fetal motion in utero with high clinical reliability, 3) For cases involving major CNS anomalies, cine MR imaging provides information on extremity motility in fetuses and serves as a prognostic indicator of postnatal outcome, and 4) The cine MR used to observe fetal activity is technically 2D and conceptually three-dimensional. It provides four-dimensional information for making proper and timely obstetrical and/or postnatal management decisions.


Improved detection of aneuploid blastocysts using a new 12-chromosome FISH test.
Fluorescence in-situ hybridization (FISH) has been the principal method used for the identification and preferential transfer of chromosomally normal embryos, in the context of both preimplantation genetic diagnosis (PGD) and screening (PGS). Generally, the probe combinations used during PGS have focused on chromosomes frequently identified as abnormal in prenatal samples or material derived from first-trimester spontaneous abortions. Recent data, however, obtained with the use of comparative genomic hybridization (CGH), have suggested that commonly used PGS strategies may fail to detect a large number of aneuploidies affecting preimplantation embryos. Some chromosomes, which have been relatively neglected in PGS protocols thus far, display a disproportionate contribution to embryo aneuploidy and should be prioritized for screening. Using CGH data, it is possible to design new probe combinations that examine between 10 and 12 chromosomes and are capable of accurately diagnosing 89-91% of anomalies seen in embryos. At present, 24-chromosome tests, such as CGH, array CGH or single nucleotide polymorphism arrays, remain relatively costly and, in some cases, are yet to be fully validated. For these reasons, a cost-effective method, capable of accurately detecting almost all aneuploid embryos, represents an attractive alternative to comprehensive chromosome screening approaches.


Characterization of Turbid Colloidal Suspensions Using Light Scattering Techniques Combined with Cross-Correlation Methods.
The ability to characterize colloidal suspensions by means of dynamic light scattering is in general limited to systems with negligible contributions from multiple scattering. For larger particle sizes with high scattering contrast this immediately limits the technique to very low concentrations. A promising solution of this problem is to suppress multiple scattering in dynamic light scattering experiments using cross-correlation schemes. Based on these considerations we have constructed a so-called 3D cross-correlation experiment with which we are able to characterize extremely turbid suspensions. We have measured monomodal and bimodal suspensions of latex particles of relatively high volume fraction. The results show clearly that we are able to measure the dynamic structure factor in concentrated polydisperse suspensions with dynamic light scattering. Combining static and dynamic light scattering measurements for characterizing turbid suspensions the single scattering particle form factor and also the static structure factor can be evaluated. We demonstrate that the implementation of a 3D cross-correlation scheme is a powerful method in suppressing multiple scattering contributions in light scattering experiments and opens a wide field of characterization of colloidal dispersions with high turbidity without having to resort to high dilution. Copyright 1998 Academic Press.


High prevalence of forced sex among non-brothel based, wine shop centered sex workers in Chennai, India.
Sexual violence has been shown to increase women's risk of HIV infection. India is a country where the HIV epidemic is growing among women and intimate partner violence (IPV) is pervasive. This study examined prevalence of and factors associated with forced sex among female sex workers (FSWs) in Chennai, India. We conducted a probability survey among FSWs in 24 slum venues and identified predictive factors for recent forced sex using univariate and multivariable proportional odds models. Among 522 FSWs, 28% reported having forced sex with one partner and 35% with 2+ partners. In the final multivariable model, women who had a high number of partners who had a strong tendency to drink alcohol before sex were more likely to have experienced forced sex, and women who had both unprotected sex with a nonspousal partner and > 20 days of alcohol consumption in the last 30 days were more likely to have experienced forced sex. Discussion about family violence with larger social networks was independently associated with lower odds of forced sex among FSWs. HIV interventions for FSWs and their clients aimed at reducing alcohol consumption and encouraging condom use could be enhanced by violence prevention interventions to facilitate discourse about sexual violence.


Soil formate regulates the fungal nitrous oxide emission pathway.
Fungal activity is a major driver in the global nitrogen cycle, and mounting evidence suggests that fungal denitrification activity contributes significantly to soil emissions of the greenhouse gas nitrous oxide (N(2)O). The metabolic pathway and oxygen requirement for fungal denitrification are different from those for bacterial denitrification. We hypothesized that the soil N(2)O emission from fungi is formate and O(2) dependent and that land use and landforms could influence the proportion of N(2)O coming from fungi. Using substrate-induced respiration inhibition under anaerobic and aerobic conditions in combination with (15)N gas analysis, we found that formate and hypoxia (versus anaerobiosis) were essential for the fungal reduction of (15)N-labeled nitrate to (15)N(2)O. As much as 65% of soil-emitted N(2)O was attributable to fungi; however, this was found only in soils from water-accumulating landforms. From these results, we hypothesize that plant root exudates could affect N(2)O production from fungi via the proposed formate-dependent pathway.


Genetic improvement of thermo-tolerance in wine Saccharomyces cerevisiae strains by a backcross approach.
During red wine fermentation, high temperatures may cause stuck fermentation by affecting the physiology of fermenting yeast. This deleterious effect is the result of the complex interaction of temperature with other physicochemical parameters of grape juice, such as sugar and lipid content. The genetic background of fermenting yeast also interacts with this complex matrix and some strains are more resistant to high temperatures than others. Here, the temperature tolerance of nine commercial starters was evaluated, demonstrating that, at high sugar concentrations, half of them are sensitive to temperature. Using a classical backcross approach, one thermo-sensitive commercial starter was genetically improved by introducing quantitative trait loci conferring resistance to temperature. With this breeding program it is possible to obtain a thermo-resistant strain sharing most of its genome with the initial commercial starter. The parental and improved strains were compared for population growth and fermentation ability in various conditions. Despite their common genetic background, these two strains showed slight physiological differences in response to environmental changes that enable identification of the key physiological parameters influencing stuck fermentation.


Evaluation of the gas stripping technique for calculation of Henry's law constants using the initial slope method for 1,2,4,5-tetrachlorobenzene, pentachlorobenzene, and hexachlorobenzene.
Henry's law constant (HLC) is an important factor used in environmental risk assessment and fate and transport models to describe mass transfer of chemical between water and air. HLCs and structure-property relationships were assessed for 1,2,4,5-tetrachlorobenzene (TeCB), pentachlorobenzene (PeCB), and hexachlorobenzene (HCB). HLCs were determined using the volatilization rate (kv) of sparged chemical at 25 °C. Despite the assumption that kv should be constant throughout the stripping duration, results indicated that kv decreased over time according to three separate slope regions. Results of ANCOVA indicate that kv is statistically different in the third slope region, which leads to the conclusion that use of the entire stripping data set would lead to biased HLCs. This decrease in kv may be attributed to desorption from sparger surfaces, which has not been considered widely in the literature. Statistical analysis was possible because of the robustness of the current experimental procedure which included numerous replications (15 total spargers) and extensive data points available to discern key slope changes. HLCs determined using the gas stripping technique were 57, 33, and 30 Pa m(3) mol(-1) for 1,2,4,5-TeCB, PeCB, and HCB, respectively. In comparison to literature values, current TeCB and HCB HLCs were within wide reference ranges spanning approximately an order of magnitude for each chemical. PeCB HLC of the current study was two times lower than the lowest reference data.


Nutritional status evaluation and nutrient intake in adult patients with pulmonary tuberculosis and their contacts.
Malnutrition is a common status in patients with tuberculosis (TB). Because TB is disseminated through the sputum of infected persons, individuals who maintain relations with a TB patient are at high risk of infection; this risk is greater when contacts present an inadequate nutritional status. The aim of this work was to analyse and compare the nutritional status and macro and micronutrient intake of TB patients and their household contacts. A cross-sectional study was carried out in TB patients from Nuevo Leon, México, and their household contacts. Thirty-nine patients diagnosed with TB and 62 contacts were evaluated. Anthropometric evaluation was performed considering weight, height, body mass index (BMI) and waist-hip ratio (WHR); nutrient intake was evaluated by applying 24-hour dietary recalls. According to anthropometric assessment, the study population showed a greater trend towards being overweight and obese; 62% of TB patients and contacts had this type of malnutrition, while only 8% of individuals were undernourished. A greater tendency towards malnutrition was observed in the TB patient group. TB patients and their contacts presented as overweight and obese. Both groups showed similar patterns in macro and micronutrient intake. Implications of deficiencies in the intake of these nutrients are discussed on the basis of their effects on individual health.


What caused the Black Death?
For the whole of the 20th century it was believed that the Black Death and all the plagues of Europe (1347-1670) were epidemics of bubonic plague. This review presents evidence that this view is incorrect and that the disease was a viral haemorrhagic fever, characterised by a long incubation period of 32 days, which allowed it to be spread widely even with the limited transport of the Middle Ages. It is suggested that haemorrhagic plague emerged from its animal host in Ethiopia and struck repeatedly at European/Asian civilisations, before appearing as the Black Death. The CCR5-Delta32 mutation confers protection against HIV-1 in an average of 10% of the people of European origin today. It is suggested that all the Deltaccr5 alleles originated from a single mutation event that occurred before 1000 BC and the subsequent epidemics of haemorrhagic plague gently forced up its frequency to 5 x 10(-5) at the time of the Black Death. Epidemics of haemorrhagic plague over the next three centuries then steadily raised the frequency in Europe (but not elsewhere) to present day values.


Design, implementation, and demographic differences of HEAL: a self-report health care leadership instrument.
The medical community has recognized the importance of leadership skills among its members. While numerous leadership assessment tools exist at present, few are specifically tailored to the unique health care environment. The study team designed a 24-item survey (Healthcare Evaluation & Assessment of Leadership [HEAL]) to measure leadership competency based on the core competencies and core principles of the Duke Healthcare Leadership Model. A novel digital platform was created for use on handheld devices to facilitate its distribution and completion. This pilot phase involved 126 health care professionals self-assessing their leadership abilities. The study aimed to determine both the content validity of the survey and the feasibility of its implementation and use. The digital platform for survey implementation was easy to complete, and there were no technical problems with survey use or data collection. With regard to reliability, initial survey results revealed that each core leadership tenet met or exceeded the reliability cutoff of 0.7. In self-assessment of leadership, women scored themselves higher than men in questions related to patient centeredness (P=0.016). When stratified by age, younger providers rated themselves lower with regard to emotional intelligence and integrity. There were no differences in self-assessment when stratified by medical specialty. While only a pilot study, initial data suggest that HEAL is a reliable and easy-to-administer survey for health care leadership assessment. Differences in responses by sex and age with respect to patient centeredness, integrity, and emotional intelligence raise questions about how providers view themselves amid complex medical teams. As the survey is refined and further administered, HEAL will be used not only as a self-assessment tool but also in "360" evaluation formats.


Early Referral to Palliative Care: The Rationing of Timely Health Care for Cancer Patients.
Palliative care in oncology is an interdisciplinary approach, centered on patients and their families, carried out along the course of neoplastic diseases, based on symptom control, assertive communication and shared decision-making. Although clinical guidelines recommend a holistic intervention, early integration of palliative care into traditional oncological treatment, research shows a great delay in referral of patients, restricting palliative care to end-of-life care. Why does there seem to be a rationing of the early referral, sometimes in violation of human dignity? To a large extent it has to do with lack of knowledge, training and education of health professionals about palliative care and the techniques to deal with the process of death and dying. Several studies have demonstrated the benefit of integrating palliative actions into the routine of active cancer treatments, not only in terms of effective control of physical and psychological symptoms, but also in terms of overall quality of life, patient and family satisfaction, health care costs and survival in some cases. It is necessary to take measures that encourage oncologists to obtain further training in palliative care, as a formal, compulsory internship, integrated in their specific training program. This way, a new generation of physicians will surely change the lives of cancer patients, and their families, integrating - without disproportionate rationing - oncology and palliative medicine.


Voltage-activated currents in guinea pig pancreatic alpha 2 cells. Evidence for Ca2+-dependent action potentials.
Glucagon-secreting alpha 2 cells were isolated from guinea pig pancreatic islets and used for electrophysiological studies of voltage-activated ionic conductances using the patch-clamp technique. The alpha 2 cells differed from beta cells in producing action potentials in the absence of glucose. The frequency of these potentials increased after addition of 10 mM arginine but remained unaffected in the presence of 5-20 mM glucose. When studying the conductances underlying the action potentials, we identified a delayed rectifying K+ current, an Na+ current, and a Ca2+ current. The K+ current activated above -20 mV and then increased with the applied voltage. The Na+ current developed at potentials above -50 mV and reached a maximal peak amplitude of 550 pA during depolarizing pulses to -15 mV. The Na+ current inactivated rapidly (tau h approximately 0.7 ms at 0 mV). Half-maximal steady state inactivation was attained at -58 mV, and currents could no longer be elicited after conditioning pulses to potentials above -40 mV. The Ca2+ current first became detectable at -50 mV and reached a maximal amplitude of 90 pA (in extracellular [Ca2+] = 2.6 mM) at about -10 mV. Unlike the Na+ current, it inactivated little or not at all. Membrane potential measurements demonstrated that both the Ca2+ and Na+ currents contribute to the generation of the action potential. Whereas there was an absolute requirement of extracellular Ca2+ for action potentials to be elicited at all, suppression of the much larger Na+ current only reduced the upstroke velocity of the spikes. It is suggested that this behavior reflects the participation of a low-threshold Ca2+ conductance in the pacemaking of alpha 2 cells.


Microbial electrosynthesis: Towards sustainable biorefineries for production of green chemicals from CO2 emissions.
Decarbonisation of the economy has become a priority at the global level, and the resulting legislative pressure is pushing the chemical and energy industries away from fossil fuels. Microbial electrosynthesis (MES) has emerged as a promising technology to promote this transition, which will further benefit from the decreasing cost of renewable energy. However, several technological challenges need to be addressed before the MES technology can reach its maturity. The aim of this review is to critically discuss the bottlenecks hampering the industrial adoption of MES, considering the whole production process (from the CO2 source to the marketable products), and indicate future directions. A flexible stack design, with flat or tubular MES modules and direct CO2 supply, is required for site-specific decentralised applications. The experience gained for scaling-up electrochemical cells (e.g. electrolysers) can serve as a guideline for realising pilot MES stacks to be technologically and economically evaluated in industrially relevant conditions. Maximising CO2 abatement rate by targeting high-rate production of acetate can promote adoption of MES technology in the short term. However, the development of a replicable and robust strategy for production and in-line extraction of higher-value products (e.g. caproic acid and hexanol) at the cathode, and meaningful exploitation of the currently overlooked anodic reactions, can further boost MES cost-effectiveness. Furthermore, the use of energy storage and smart electronics can alleviate the fluctuations of renewable energy supply. Despite the unresolved challenges, the flexible MES technology can be applied to decarbonise flue gas from different sources, to upgrade industrial and wastewater treatment plants, and to produce a wide array of green and sustainable chemicals. The combination of these benefits can support the industrial adoption of MES over competing technologies.


Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden.
Although the heritability of atrial fibrillation (AF) has been determined, the relevance of family history of AF for the likelihood of recurrent hospitalization for AF is unknown. The aim of this nationwide study was to determine whether family history of AF is a risk factor of recurrent hospitalization for lone AF (LAF), i.e., AF with unknown etiology. The familial risk for first time LAF hospitalization was also determined and compared to the risk of recurrent hospitalization for LAF. We examined whether family history of AF is a risk factor for recurrent hospitalization for LAF in the whole Swedish population. We linked Multigeneration Register data on individuals aged 0-60 years to Hospital Discharge Register data for the period 1987-2009 to compare LAF recurrent hospitalization risk among individuals with and without parental or sibling history of AF. We calculated hazard ratios (HRs) to determine the familial HR of recurrent hospitalization for LAF. Odds ratios (OR) were calculated for familial risk of first time LAF hospitalization. The risk of recurrent LAF hospitalization was 1.23 (95% CI 1.17-1.30) for individuals with affected parents compared to 1.30 (95% CI 1.22-1.38) for those with affected siblings. After 10 years of follow up 50% of those without and 60% of those with family history had recurrent hospitalization for LAF. The risk of recurrent LAF hospitalization in individuals with two affected parents was 1.65 (95% CI 1.44-1.90). There was an interaction between age and family history, with family history having a weaker effect on LAF hospitalization risk in older age groups. The OR for first time LAF hospitalization was 2.08 (95% CI 2.02-2.15) for offspring with affected parents and 3.23 (95% CI 3.08-3.39) for individuals with affected siblings. Family history of AF is a novel risk factor for recurrent LAF hospitalization. The higher recurrence hospitalization risk in multiplex families and younger individuals suggests a genetic contribution. However, the familial risk for recurrent LAF hospitalization was much lower than the risk for first time LAF hospitalization, suggesting that familial and possibly genetic factors are more important for first time LAF hospitalization than recurrent LAF hospitalization.


Preoperative Assessment in Older Adults: A Comprehensive Approach.
Surgical outcomes are significantly influenced by patients' overall health, function, and life expectancy. A comprehensive geriatric preoperative assessment of older adults requires expanding beyond an organ-based or disease-based assessment. At a preoperative visit, it is important to establish the patient's goals and preferences, and to determine whether the risks and benefits of surgery match these goals and preferences. These discussions should cover the possibility of resuscitation and ventilator support, prolonged rehabilitation, and loss of independence. The assessment should include evaluation of medical comorbidities, cognitive function, decision-making capacity, functional status, fall risk, frailty, nutritional status, and potentially inappropriate medication use. Problems identified in any of these key areas are associated with an increased risk of postoperative complications, institutionalization, functional decline, and, in some cases, mortality. If a patient elects to proceed with surgery, the risks should be communicated to surgical teams to allow for inpatient interventions that lower the risk of postoperative complications and functional decline, such as early mobilization and limiting medications that can cause delirium. Alcohol abuse and smoking are associated with increased rates of postoperative complications, and physicians should discuss cessation with patients before surgery. Physicians should also assess patients' social support systems because they are a critical component of discharge planning in this population and have been shown to predict 30-day postoperative morbidity.


Hierarchical cluster analysis of labour market regulations and population health: a taxonomy of low- and middle-income countries.
An important contribution of the social determinants of health perspective has been to inquire about non-medical determinants of population health. Among these, labour market regulations are of vital significance. In this study, we investigate the labour market regulations among low- and middle-income countries (LMICs) and propose a labour market taxonomy to further understand population health in a global context. Using Gross National Product per capita, we classify 113 countries into either low-income (n = 71) or middle-income (n = 42) strata. Principal component analysis of three standardized indicators of labour market inequality and poverty is used to construct 2 factor scores. Factor score reliability is evaluated with Cronbach's alpha. Using these scores, we conduct a hierarchical cluster analysis to produce a labour market taxonomy, conduct zero-order correlations, and create box plots to test their associations with adult mortality, healthy life expectancy, infant mortality, maternal mortality, neonatal mortality, under-5 mortality, and years of life lost to communicable and non-communicable diseases. Labour market and health data are retrieved from the International Labour Organization's Key Indicators of Labour Markets and World Health Organization's Statistical Information System. Six labour market clusters emerged: Residual (n = 16), Emerging (n = 16), Informal (n = 10), Post-Communist (n = 18), Less Successful Informal (n = 22), and Insecure (n = 31). Primary findings indicate: (i) labour market poverty and population health is correlated in both LMICs; (ii) association between labour market inequality and health indicators is significant only in low-income countries; (iii) Emerging (e.g., East Asian and Eastern European countries) and Insecure (e.g., sub-Saharan African nations) clusters are the most advantaged and disadvantaged, respectively, with the remaining clusters experiencing levels of population health consistent with their labour market characteristics. The labour market regulations of LMICs appear to be important social determinant of population health. This study demonstrates the heuristic value of understanding the labour markets of LMICs and their health effects using exploratory taxonomy approaches.


Combinatorial guidance by CCR7 ligands for T lymphocytes migration in co-existing chemokine fields.
Chemokines mediate the trafficking and positioning of lymphocytes in lymphoid tissues that is crucial for immune surveillance and immune responses. In particular, a CCR7 ligand, CCL21, plays important roles in recruiting T cells to secondary lymphoid tissues (SLT). Furthermore, CCL21 together with another CCR7 ligand, CCL19, direct the navigation and compartmentation of T cells within SLT. However, the distinct roles of these two chemokines for regulating cell trafficking and positioning are not clear. In this study, we explore the effect of co-existing CCL19 and CCL21 concentration fields on guiding T cell migration. Using microfluidic devices that can configure single and superimposed chemokine fields we show that under physiological gradient conditions, human peripheral blood T cells chemotax to CCL21 but not CCL19. Furthermore, T cells migrate away from the CCL19 gradient in a uniform background of CCL21. This repulsive migratory response is predicted by mathematical modeling based on the competition of CCL19 and CCL21 for CCR7 signaling and the differential ability of the two chemokines for desensitizing CCR7. These results suggest a new combinatorial guiding mechanism by CCL19 and CCL21 for the migration and trafficking of CCR7 expressing leukocytes.


Atomic-scale observation of pressure-dependent reduction dynamics of W18O49 nanowires using environmental TEM.
The real-time observation of structural evolution of materials can provide critical information for understanding their reduction mechanisms under different environments. Herein, we report the atomic-scale observation of the reduction dynamics of W18O49 nanowires (NWs) using environmental transmission electron microscopy. Intriguingly, the reduction pathway is found to be affected by oxygen pressure. Under high oxygen pressure (∼0.095 Pa), a W18O49 NW epitaxially transforms into a WO2 NW via mass transport across the interface between (010)W18O49 and (101)WO2. While under low oxygen pressure (∼0.0004 Pa), the transformation follows the sequence of W18O49(NW) → WO2(NW) → β-W(nanoparticles), which is identified as a new reduction pathway. These findings reveal the pressure-dependent reduction and a new transformation pathway, and extend our current understanding of the reduction dynamics of metal oxides.


School-level intraclass correlation for physical activity in adolescent girls.
The Trial for Activity in Adolescent Girls (TAAG) is a multi-center group-randomized trial to reduce the usual decline in moderate to vigorous physical activity (MVPA) among middle-school girls. In group-randomized trials, the group-level intraclass correlation (ICC) has a strong inverse relationship to power and a good estimate of ICC is needed to determine sample size. As a result, we conducted a substudy to estimate the school-level ICC for intensity-weighted minutes of MVPA measured using an accelerometer. To estimate the ICC, each of six sites recruited two schools and randomly selected 45 eighth grade girls from each school; 80.7% participated. Each girl wore an Actigraph accelerometer for 7 d. Readings above 1500 counts per half minute were counted as MVPA. These counts were converted into metabolic equivalents (MET) and summed over 6 a.m. to midnight to provide MET-minutes per 18-h day of MVPA. Minutes of MVPA per 18-h day also were calculated ignoring the MET value. The unadjusted school-level ICC for minutes of MVPA was 0.0205 (95%CI: -0.0079, 0.1727) and for MET-minutes of MVPA was 0.0045 (95% CI: -0.0147, 0.1145). Adjustment for age and BMI had no measurable effect, whereas adjustment for ethnicity reduced both ICC; adjusted values were 0.0175 (95% CI: -0.0092, 0.1622) for minutes of MVPA and 0.0000 (95% CI: -0.0166, 0.0968) for MET-minutes of MVPA. This information was used to calculate the number of schools and girls needed for TAAG to have 90% power to detect a 50% reduction in the decline of MET-minutes of MVPA between sixth and eighth grade. The results called for 36 schools in TAAG, with 120 girls invited for measurements at each school, and a minimum participation rate of 80%.


Alterations in glycoprotein synthesis and guanosine triphosphate levels associated with the differentiation of HL-60 leukemia cells produced by inhibitors of inosine 5'-phosphate dehydrogenase.
The synthetic "C" nucleoside, tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), its selenium analogue selenazofurin, and the related inhibitor of inosine 5'-phosphate (IMP) dehydrogenase, mycophenolic acid, are effective inducers of the terminal differentiation of HL-60 promyelocytic leukemia cells. The inhibition of cellular replication and the induced maturation produced by these agents appears to be a consequence of the inhibition of IMP dehydrogenase, since growth inhibition is partially reversed and differentiation is completely prevented by the simultaneous exposure of cells treated with inhibitors of IMP dehydrogenase to exogenous guanosine, which serves to circumvent the effects of the blockage of IMP dehydrogenase. The exposure of HL-60 leukemia cells to inhibitors of IMP dehydrogenase caused a marked reduction in the incorporation of [3H]mannose into both cellular glycoproteins and their lipid-linked oligosaccharide precursors; these effects are presumably due to the pronounced decrease in intracellular levels of guanosine triphosphate produced by blockage of IMP dehydrogenase. Maximum effects on glycoprotein biosynthesis occurred within 8 h of exposure to the inhibitors of IMP dehydrogenase. The simultaneous incubation of cells with guanosine and these inducers of differentiation partially prevented the reduction in [3H]mannose incorporation into glycoproteins, supporting a relationship between glycoprotein biosynthesis and guanosine triphosphate formation in the induction of differentiation by inhibitors of IMP dehydrogenase.


Methods for Single-Cell Pulse-Chase Analysis of Nuclear Components.
Pulse-chase methods offer powerful tools for following the evolution of a biological system over time, but are usually limited to ensemble measurements of the average behavior of very large numbers of cells. Here we describe three methods ranging from a true pulse-chase, through selective regional photoactivation, to pharmacological induction of an altered protein state, which can be applied to time-dependent studies at the single-cell level. These methods are exemplified by experimental protocols to follow region-selective nuclear envelope targeting of nascent phospholipids, a nascent nuclear lamin protein (lamin B1), and an immature lamin precursor (prelamin A).


HCT116 colonospheres shows elevated expression of hTERT and β-catenin protein - a short report.
Clonospheres formed due to modified culture conditions are often studied for their stem cell like behaviour. The main objective of the current study is to compare the stem cell markers and link it to hTERT levels by monitoring their quantitative gene expression as they are potential targets for new generation combination therapeutics. In the present study we created stable colonospheres of Human colon cancer cell line HCT-116 long term culture conditions of Serum deprivation. Clonospheres formed after 15 days were collected by gentle and enzymatic dissociation was performed. Single cell suspension was obtained by mechanically dissociating the cells through a 22G needle. Single cells were replanted at a density 1200 cells/ml in Serum Free Medium in the 6 well plates for further passage. Passaging of cells was done at an interval of 8 days. The spheres formed were cyto-spun in special slides for Immunocytochemistry (ICC) studies for β-catenin protein and hTERT. The colonospheres were also processed for real time PCR expression studies for the same genes to confirm. In this present study, immunofluorescence studies revealed high β-catenin expression in the nucleus in colonospheres as compared to that of differentiated cancer cell line HCT-116 where the signal was localized mostly in the membranous and non-nuclear regions. Also increased TRF2 signal in colonospheres indicated higher activity of hTERT gene as TRF2 is the direct activator of hTERT to protect the telomere. Quantitative PCR studies showed that there was a significant over expression (p<0.05) at the mRNA level of the hTERT, TRF2, Rap1 genes along with the β-catenin over expression. Immunofluorescence analysis also revealed higher expression of CSC marker CD44 and ALDH1in colonospheres compared to the parental population. Clonospheres sub-population is showing higher degree of hTERT gene expression along with β-catenin when compared to the parental HCT-116 cancer cells. We also checked the co expression of other telomere maintenance genes mainly TRF 2 and Rap1 which also showed similar results. Therefore, we conclude that not only hTERT but possibly other Sheltrin proteins are regulated by β-catenin which is co expressed.


Theoretical Determination of Band Edge Alignments at the Water-CuInS2(112) Semiconductor Interface.
Knowledge of a semiconductor electrode's band edge alignment is essential for optimizing processes that occur at the semiconductor/electrolyte interface. Photocatalytic processes are particularly sensitive to such alignments, as they govern the transfer of photoexcited electrons or holes from the surface to reactants in the electrolyte solution. Reconstructions of a semiconductor surface during operation, as well as its interaction with the electrolyte solution, must be considered when determining band edge alignment. Here, we employ density functional theory + U theory to assess the stability of reconstructed CuInS2 surfaces, a system which has shown promise for the active and selective photoelectrocatalytic reduction of CO2 to CH3OH. Using many-body Green's function theory combined with calculations of surface work functions, we determine band edge positions of explicitly solvated, reconstructed CuInS2 surfaces. We find that there is a linear relationship between band edge position and net surface dipole, with the most stable solvent/surface structures tending to minimize this dipole because of generally weak interactions between the surface and solvating water molecules. We predict a conduction band minimum (CBM) of the solvated, reconstructed CuInS2 surface of -2.44 eV vs vacuum at the zero-dipole intercept of the dipole/CBM trendline, in reasonable agreement with the experimentally reported CBM position at -2.64 eV vs vacuum. This methodology offers a simplified approach for approximating the band edge positions at complex semiconductor/electrolyte interfaces.


Substrate-Induced Nanoscale Undulations of Borophene on Silver.
Two-dimensional (2D) materials tend to be mechanically flexible yet planar, especially when adhered on metal substrates. Here, we show by first-principles calculations that periodic nanoscale one-dimensional undulations can be preferred in borophenes on concertedly reconstructed Ag(111). This "wavy" configuration is more stable than its planar form on flat Ag(111) due to anisotropic high bending flexibility of borophene that is also well described by a continuum model. Atomic-scale ultrahigh vacuum scanning tunneling microscopy characterization of borophene grown on Ag(111) reveals such undulations, which agree with theory in terms of topography, wavelength, Moiré pattern, and prevalence of vacancy defects. Although the lattice is coherent within a borophene island, the undulations nucleated from different sides of the island form a distinctive domain boundary when they are laterally misaligned. This structural model suggests that the transfer of undulated borophene onto an elastomeric substrate would allow for high levels of stretchability and compressibility with potential applications to emerging stretchable and foldable devices.


Control of breathing by "nerve glue".
Long regarded as mere structural support for neurons, neuroglial cells are now considered pivotal for brain metabolism, the blood-brain barrier, cerebral hemodynamics, and neuronal function. Multitasking by glia involves numerous signaling and effector pathways that control various processes, including neurotransmitter uptake and release of gliotransmitters, such as glutamate or adenosine 5'-triphosphate (ATP). Acidosis of cerebrospinal fluid causes ATP release from astrocytic glia at the ventral brainstem surface, which excites neighboring brainstem neurons that stimulate neurons in the pre-Bötzinger complex (preBötC), which controls inspiratory breathing movements. New insights into glial regulation of complex behavior, and particularly into respiratory circuit function, are evolving from application of genetically engineered optical stimulation and Ca(2+) imaging tools, combined with other molecular and electrophysiological approaches. These advances in technology will enable direct analyses of respiratory-related neuron-glia interactions not only at the ventral brainstem surface but also within the preBötC, which generates a vital brain rhythm.


Factors influencing lower esophageal sphincter relaxation after deglutition.
To study the relationship between upper esophageal sphincter (UES) relaxation, peristaltic pressure and lower esophageal sphincter (LES) relaxation following deglutition in non-dysphagic subjects. Ten non-dysphagic adult subjects had a high-resolution manometry probe passed transnasally and positioned to cover the UES, the esophageal body and the LES. Ten water swallows in each subject were analyzed for time lag between UES relaxation and LES relaxation, LES pressure at time of UES relaxation, duration of LES relaxation, the distance between the transition level (TL) and the LES, time in seconds that the peristaltic wave was before (negative value) or after the TL when the LES became relaxed, and the maximal peristaltic pressure in the body of the esophagus. Relaxation of the LES occurred on average 3.5 s after the bolus had passed the UES and in most cases when the peristaltic wave front had reached the TL. The LES remained relaxed until the peristaltic wave faded away above the LES. LES relaxation seemed to be caused by the peristaltic wave pushing the bolus from behind against the LES gate.


Content and implementation of clinical decisions in the routine care of people with severe mental illness.
Clinical decision making (CDM) in the treatment of people with severe mental illness relates to a wide range of life domains. To examine content of CDM in mental health care from the perspectives of service users and staff and to investigate variation in implementation of decisions for differing content. As part of the European multicenter study clinical decision making and outcome in routine care for people with severe mental illness (ISRCTN75841675), 588 service users and their clinicians were asked to identify the decisions made during their last meeting. Decisions were then coded into content categories. Two months later, both parties reported if these decisions had been implemented. Agreement between patients and staff regarding decision making was moderate (k = 0.21–0.49; p < 0.001). Decisions relating to medication and social issues were most frequently identified. Overall reported level of implementation was 73.5% for patients and 74.7% for staff, and implementation varied by decision content. A variety of relevant decision topics were shown for mental health care.Implementation rates varied in relation to topic and may need different consideration within the therapeutic dyad.


The N-terminus of the norepinephrine transporter regulates the magnitude and selectivity of the transporter-associated leak current.
The norepinephrine (NE) transporter (NET) mediates the removal of NE from synaptic spaces and is a major target for antidepressants, amphetamine and cocaine. Previously, we have shown that syntaxin 1A (SYN 1A) supports human NET (hNET) cell surface expression, that hNET/SYN 1A interactions are direct and mediated by the hNET N-terminus, and that the hNET/SYN 1A association limits substrate-induced hNET-associated currents [Sung, U., Apparsundaram, S., Galli, A., Kahlig, K.M., Savchenko, V., Schroeter, S., Quick, M.W., Blakely, R.D., 2003. A regulated interaction of syntaxin 1A with the antidepressant-sensitive norepinephrine transporter establishes catecholamine clearance capacity. J. Neurosci. 23, 1697-1709]. These data raise the possibility that the hNET N-terminus, and potentially its interaction with SYN 1A, might regulate other hNET conductance states, including the hNET-mediated leak current. Importantly for monoamine transporters, the leak conductance has been shown to play a critical role in regulating cell membrane potential and possibly neuronal excitability [Quick, M.W., 2003. Regulating the conducting states of a mammalian serotonin transporter. Neuron 40, 537-549]. Here we demonstrate that deletion of the binding domain for SYN 1A in the NET N-terminus robustly enhances the NET-mediated leak current as well as its selectivity for Cl- permeation under particular intracellular ionic compositions. In addition, we show that the NET N-terminus coordinates the ability of intracellular Na+ and Cl- to regulate the leak conductance. These data suggest that the NET N-terminus regulates and defines the ionic specificity of the NET-mediated leak current.