Dissolution dominating calcification process in polar pteropods close to the point of aragonite undersaturation

Thecosome pteropods are abundant upper-ocean zooplankton that build aragonite shells. Ocean acidification results in the lowering of aragonite saturation levels in the surface layers, and several incubation studies have shown that rates of calcification in these organisms decrease as a result. This study provides a weight-specific net calcification rate function for thecosome pteropods that includes both rates of dissolution and calcification over a range of plausible future aragonite saturation states (Omega_Ar). We measured gross dissolution in the pteropod Limacina helicina antarctica in the Scotia Sea (Southern Ocean) by incubating living specimens across a range of aragonite saturation states for a maximum of 14 days. Specimens started dissolving almost immediately upon exposure to undersaturated conditions (Omega_Ar,0.8), losing 1.4% of shell mass per day. The observed rate of gross dissolution was different from that predicted by rate law kinetics of aragonite dissolution, in being higher at Var levels slightly above 1 and lower at Omega_Ar levels of between 1 and 0.8. This indicates that shell mass is affected by even transitional levels of saturation, but there is, nevertheless, some partial means of protection for shells when in undersaturated conditions. A function for gross dissolution against Var derived from the present observations was compared to a function for gross calcification derived by a different study, and showed that dissolution became the dominating process even at Omega_Ar levels close to 1, with net shell growth ceasing at an Omega_Ar of 1.03. Gross dissolution increasingly dominated net change in shell mass as saturation levels decreased below 1. As well as influencing their viability, such dissolution of pteropod shells in the surface layers will result in slower sinking velocities and decreased carbon and carbonate fluxes to the deep ocean

The identification of informative genes from multiple datasets with increasing complexity

Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

The impact of seawater saturation state and bicarbonate ion concentration on calcification by new recruits of two Atlantic corals

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Coral Reefs 30 (2011): 321-328, doi:10.1007/s00338-010-0697-z.Rising concentrations of atmospheric CO2 are changing the carbonate chemistry of the oceans, a process known as ocean acidification (OA). Absorption of this CO2 by the surface oceans is increasing the amount of total dissolved inorganic carbon (DIC) and bicarbonate ion (HCO3 -) available for marine calcification, yet is simultaneously lowering the seawater pH and carbonate ion concentration ([CO3 2-]), and thus the saturation state of seawater with respect to aragonite (Ωar). We investigated the relative importance of [HCO3 -] versus [CO3 2-] for early calcification by new recruits (primary polyps settled from zooxanthellate larvae) of two tropical coral species, Favia fragum and Porites astreoides. The polyps were reared over a range of Ωar values, which were manipulated by both acid-addition at constant pCO2 (decreased total [HCO3 -] and [CO3 2-]) and by pCO2 elevation at constant alkalinity (increased [HCO3 -], decreased [CO3 2-]). Calcification after two weeks was quantified by weighing the complete skeleton (corallite) accreted by each polyp over the course of the experiment. Both species exhibited the same negative response to decreasing [CO3 2-] whether Ωar was lowered by acid-addition or by pCO2 elevation - calcification did not follow total DIC or [HCO3 -]. Nevertheless, the calcification response to decreasing [CO3 2-] was non-linear. A statistically significant decrease in calcification was only detected between Ωar = < 2.5 and Ωar = 1.1 – 1.5, where calcification of new recruits was reduced by 22 – 37 % per 1.0 decrease in Ωar. Our results differ from many previous studies that report a linear coral calcification response to OA, and from those showing that calcification increases with increasing [HCO3 -]. Clearly, the coral calcification response to OA is variable and complex. A deeper understanding of the biomineralization mechanisms and environmental conditions underlying these 3 variable responses is needed to support informed predictions about future OA impacts on corals and coral reefs.This study was supported by NSF award 0648157 (Cohen and McCorkle), NSF 1041106 (Cohen, McCorkle), NSF 1041052 (de Putron), the VITA foundation (de Putron), WHOI Ocean Life Institute (Cohen), PEI and EEB Departments at Princeton University, Bill and Anne Charrier, and the Anthony B. Evnin, Dean’s Roundtable, and Edmund Hayes Sr. senior thesis funds (Dillon)

Quantifying the Adaptive Potential of an Antibiotic Resistance Enzyme

For a quantitative understanding of the process of adaptation, we need to understand its “raw material,” that is, the frequency and fitness effects of beneficial mutations. At present, most empirical evidence suggests an exponential distribution of fitness effects of beneficial mutations, as predicted for Gumbel-domain distributions by extreme value theory. Here, we study the distribution of mutation effects on cefotaxime (Ctx) resistance and fitness of 48 unique beneficial mutations in the bacterial enzyme TEM-1 β-lactamase, which were obtained by screening the products of random mutagenesis for increased Ctx resistance. Our contributions are threefold. First, based on the frequency of unique mutations among more than 300 sequenced isolates and correcting for mutation bias, we conservatively estimate that the total number of first-step mutations that increase Ctx resistance in this enzyme is 87 [95% CI 75–189], or 3.4% of all 2,583 possible base-pair substitutions. Of the 48 mutations, 10 are synonymous and the majority of the 38 non-synonymous mutations occur in the pocket surrounding the catalytic site. Second, we estimate the effects of the mutations on Ctx resistance by determining survival at various Ctx concentrations, and we derive their fitness effects by modeling reproduction and survival as a branching process. Third, we find that the distribution of both measures follows a Fréchet-type distribution characterized by a broad tail of a few exceptionally fit mutants. Such distributions have fundamental evolutionary implications, including an increased predictability of evolution, and may provide a partial explanation for recent observations of striking parallel evolution of antibiotic resistance

Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease

BACKGROUND: Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women. METHODS: A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO(2 )and transcutaneous PCO(2 )(tcCO(2)) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA. RESULTS: Thirteen patients completed the trial. At baseline, the average ± SD of SaO(2 )mean was 90.6 ± 3.2 % and the median of SaO(2 )nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 ± 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO(2 )median was 6.0 ± 0.9 kPa and decreased with MPA by 0.9 ± 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO(2 )nadir and tcCO(2 )median also during REM sleep. Three weeks after cessation of MPA, the SaO(2 )mean remained 1.4 ± 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO(2 )nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO(2 )mean and SaO(2 )nadir during sleep with MPA were inversely associated with baseline SaO(2 )mean (r = -0.70, p = 0.032) and baseline SaO(2 )nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO(2 )mean, SaO(2 )nadir and tcCO(2 )levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables. CONCLUSION: MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO(2 )values. Long-term studies in females are warranted

Horizontal gene transfer dynamics and distribution of fitness effects during microbial in silico evolution

<p>Abstract</p> <p>Background</p> <p>Horizontal gene transfer (HGT) is a process that facilitates the transfer of genetic material between organisms that are not directly related, and thus can affect both the rate of evolution and emergence of traits. Recent phylogenetic studies reveal HGT events are likely ubiquitous in the Tree of Life. However, our knowledge of HGT's role in evolution and biological organization is very limited, mainly due to the lack of ancestral evolutionary signatures and the difficulty to observe complex evolutionary dynamics in a laboratory setting. Here, we utilize a multi-scale microbial evolution model to comprehensively study the effect of HGT on the evolution of complex traits and organization of gene regulatory networks.</p> <p>Results</p> <p>Large-scale simulations reveal a distinct signature of the Distribution of Fitness Effect (DFE) for HGT events: during evolution, while mutation fitness effects become more negative and neutral, HGT events result in a balanced effect distribution. In either case, lethal events are significantly decreased during evolution (33.0% to 3.2%), a clear indication of mutational robustness. Interestingly, evolution was accelerated when populations were exposed to correlated environments of increasing complexity, especially in the presence of HGT, a phenomenon that warrants further investigation. High HGT rates were found to be disruptive, while the average transferred fragment size was linked to functional module size in the underlying biological network. Network analysis reveals that HGT results in larger regulatory networks, but with the same sparsity level as those evolved in its absence. Observed phenotypic variability and co-existing solutions were traced to individual gain/loss of function events, while subsequent re-wiring after fragment integration was necessary for complex traits to emerge.</p

A pilot feasibility trial of alcohol screening and brief intervention in the police custody setting (ACCEPT): study protocol for a cluster randomised controlled trial

BACKGROUND: There is evidence of an association between alcohol use and offending behaviour and around a quarter of police time is spent on alcohol-related incidents. Police custody, therefore, provides an important opportunity to intervene. This pilot trial aims to investigate whether a definitive evaluation of screening and brief interventions aimed at reducing risky drinking in arrestees is acceptable and feasible in the custody suite setting. METHODS: Screening will be carried out by trained detention officers or drug and alcohol workers in four police forces across two geographical areas (North East and South West England). Detention officers (or drug and alcohol workers) will be cluster randomised to one of three conditions: screening only (control group), screening followed immediately by 10 min of manualised brief structured advice delivered by the individual responsible for screening (intervention 1) or screening followed by 10 min of manualised brief structured advice delivered by the individual responsible for screening plus the offer of a subsequent 20-min session of behaviour change counselling delivered by a trained alcohol health worker (intervention 2). Participants will be arrestees aged 18+ who screen positive on the Alcohol Use Disorders Identification Test. Participants will be followed up at 6 and 12 months post-intervention. An embedded qualitative process evaluation will explore acceptability of alcohol screening and brief intervention to staff and arrestees as well as facilitators and barriers to the delivery of such approaches in this setting. RESULTS: Recruitment is currently underway and due to end May 2015. CONCLUSION: Results from this pilot trial will determine if a definitive evaluation is possible in the future and will provide stakeholder input to its design. TRIAL REGISTRATION: Reference number: ISRCTN89291046

Genetic Architecture of Hybrid Male Sterility in Drosophila: Analysis of Intraspecies Variation for Interspecies Isolation

Background: The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. Methodology/Principal Findings: Isofemale strains of D. mojavensis vary significantly in their production of sterile F 1 sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL) mapping analyses directly on F1 hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS) in the F1 is complex, involving multiple QTL, epistasis, and cytoplasmic effects. Conclusions/Significance: The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C