PartitionFinder 2: New Methods for Selecting Partitioned Models of Evolution for Molecular and Morphological Phylogenetic Analyses.

PartitionFinder 2 is a program for automatically selecting best-fit partitioning schemes and models of evolution for phylogenetic analyses. PartitionFinder 2 is substantially faster and more efficient than version 1, and incorporates many new methods and features. These include the ability to analyze morphological datasets, new methods to analyze genome-scale datasets, new output formats to facilitate interoperability with downstream software, and many new models of molecular evolution. PartitionFinder 2 is freely available under an open source license and works on Windows, OSX, and Linux operating systems. It can be downloaded from www.robertlanfear.com/partitionfinder. The source code is available at https://github.com/brettc/partitionfinder.

Estimation of QT interval prolongation through model-averaging.

The current method to analyze concentration-QT interval data, which is based on predictions conditional on a best model, fails to take into account the uncertainty of the model. Previous studies have suggested that failure to take into account model uncertainty using a best model approach can result in confidence intervals that are overly optimistic and may be too narrow. Theoretically, more realistic estimates are obtained using model-averaging where the overall point estimate and confidence interval are a weighted-average from a set of candidate models, the weights of which are equal to each model's Akaike weight. Monte Carlo simulation was used to determine the degree of narrowness in the confidence interval for the degree of QT prolongation under a single ascending dose and thorough QT trial design. Results showed that model averaging performed as well as the best model approach under most conditions with no numeric advantage to using a model averaging approach. No difference was observed in the coverage of the confidence intervals when the best model and model averaging was done by AIC, AICc, or BIC, although in certain circumstances the coverage of the confidence interval themselves tended to be too narrow when using BIC. Modelers can continue to use the best model approach for concentration-QT modeling with confidence, although model averaging may offer more face validity, may be of value in cases where there is uncertainty or misspecification in the best model, and be more palatable to a non-technical reviewer than the best model approach.

Rodent-avoidance, topography and forest structure shape territory selection of a forest bird.

BACKGROUND: Understanding the factors underlying habitat selection is important in ecological and evolutionary contexts, and crucial for developing targeted conservation action in threatened species. However, the key factors associated to habitat selection often remain poorly known. We evaluated hypotheses related to abiotic and biotic factors thought to affect territory selection of the wood warbler Phylloscopus sibilatrix, a passerine living in an unpredictable environment owing to irregular rodent outbreaks and showing long-term declines particularly in Western Europe. RESULTS: Comparing breeding territories to unoccupied areas located close-by revealed that territory occupancy in north-western Switzerland was positively related to slope steepness (topographic hypothesis supported) as well as to numbers of tussocks and trees, respectively, while it showed a unimodal relationship to cover of herb layer (forest structure hypothesis supported). Furthermore, a strong negative correlation between breeding territory occupancy and rodent numbers was found, suggesting that wood warblers avoid areas with high rodent densities (rodent-avoidance hypothesis supported). Comparing breeding territories to abandoned territories showed that breeding territories were located on steeper slopes (topography hypothesis supported), at larger distance from the forest edge (anthropogenic disturbance hypothesis supported) and harboured more trees (forest structure hypothesis supported) than abandoned territories. CONCLUSIONS: Aside from structural and topographic features of the habitat, wood warblers are affected by rodent numbers when settling, making habitat selection unpredictable from year to year. Forestry practices promoting relatively high tree densities, few bushes and an intermediate low-growing ground vegetation cover would enhance habitat quality for this declining passerine. In contrast, forestry practices aiming at increasing light in forests (selective thinning, group-felling) or keeping forest stands permanently covered with shrubs, bushes and trees of various sizes (continuous cover forestry) do not benefit the wood warbler.

Exploring the potential of Diplosphaera mucosa VSPA for the treatment of petroleum effluent with simultaneous lipid production.

The discovery of unexplored, robust microalgal strains will assist in treating highly polluted industrial effluent, including petroleum effluent. In the current analysis, a newly isolated microalgal strain, Diplosphaera mucosa VSPA, was used to treat petroleum effluent in a lab-scale raceway bioreactor. Its treatment efficiency was compared with a well-known species, Chlorella pyrenoidosa. The D. mucosa VSPA strain proliferated in petroleum effluent at a high growth rate, with final biomass, and lipid concentrations reaching 6.93 g/L and 2.72 g/L, respectively. Treatment efficiency was calculated based on the final removal efficiency of ammonium nitrogen, phosphate phosphorus, and chemical oxygen demand, which was more than 90%. Control experiments suggested that the maximum removal of pollutants from petroleum effluent was due to microalgae growth. Some growth models, including the Gompertz, Logistic, Stannard, Richard, and Schnute, were used to simulate the experimental data, verifying the results. Good fitting of all models was obtained, with the R2 value reaching more than 0.90. The development of a suitable model can help in decreasing the efforts required for the scale-up of the process.

BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αß CD8+ T cells.

BCL11B, an essential transcription factor for thymopoiesis, regulates also vital processes in post-thymic lymphocytes. Increased expression of BCL11B was recently correlated with the maturation of NK cells, whereas reduced BCL11B levels were observed in native and induced T cell subsets displaying NK cell features. We show that BCL11B-depleted CD8+ T cells stimulated with IL-15 acquired remarkable innate characteristics. These induced innate CD8+ (iiT8) cells expressed multiple innate receptors like NKp30, CD161, and CD16 as well as factors regulating migration and tissue homing while maintaining their T cell phenotype. The iiT8 cells effectively killed leukemic cells spontaneously and neuroblastoma spheroids in the presence of a tumor-specific monoclonal antibody mediated by CD16 receptor activation. These iiT8 cells integrate the innate natural killer cell activity with adaptive T cell longevity, promising an interesting therapeutic potential. Our study demonstrates that innate T cells, albeit of limited clinical applicability given their low frequency, can be efficiently generated from peripheral blood and applied for adoptive transfer, CAR therapy, or combined with therapeutic antibodies.

Impacts of Salt Stress on Locomotor and Transcriptomic Responses in the Intertidal Gastropod Batillaria attramentaria.

Salinity is one of the most crucial environmental factors that structures biogeographic boundaries of aquatic organisms, affecting distribution, abundance, and behavior. However, the association between behavior and gene regulation underlying acclimation to changes in salinity remains poorly understood. In this study, we investigated the effects of salinity stress on behavior (movement distance) and patterns of gene expression (using RNA sequencing) of the intertidal gastropod Batillaria attramentaria. We examined responses to short-term (1-hour) and long-term (30-day) acclimation to a range of salinities (43, 33 [control], 23, 13, and 3 psu). We found that the intertidal B. attramentaria is able to tolerate a broad range of salinity from 13 to 43 psu but not the acute low salinity of 3 psu. Behavioral experiments showed that salt stress significantly influenced snails' movement, with lower salinity resulting in shorter movement distance. Transcriptomic analyses revealed critical metabolic pathways and genes potentially involved in acclimation to salinity stress, including ionic and osmotic regulation, signal and hormonal transduction pathways, water exchange, cell protection, and gene regulation or epigenetic modification. In general, our study presents a robust, integrative laboratory-based approach to investigate the effects of salt stress on a nonmodel gastropod facing detrimental consequences of environmental change. The current genetic results provide a wealth of reference data for further research on mechanisms of ionic and osmotic regulation and adaptive evolution of this coastal gastropod.

Simultaneous comparisons of treatments at multiple time points: Combined marginal models versus joint modeling.

We discuss several aspects of multiple inference in longitudinal settings, focusing on many-to-one and all-pairwise comparisons of (a) treatment groups simultaneously at several points in time, or (b) time points simultaneously for several treatments. We assume a continuous endpoint that is measured repeatedly over time and contrast two basic modeling strategies: fitting a joint model across all occasions (with random effects and/or some residual covariance structure to account for heteroscedasticity and serial dependence), and a novel approach combining a set of simple marginal, i.e. occasion-specific models. Upon parameter and covariance estimation with either modeling approach, we employ a variant of multiple contrast tests that acknowledges correlation between time points and test statistics. This method provides simultaneous confidence intervals and adjusted p-values for elementary hypotheses as well as a global test decision. We compare via simulation the powers of multiple contrast tests based on a joint model and multiple marginal models, respectively, and quantify the benefit of incorporating longitudinal correlation, i.e. the advantage over Bonferroni. Practical application is illustrated with data from a clinical trial on bradykinin receptor antagonism.

Evaluation of blood-brain barrier and blood-cerebrospinal fluid barrier permeability of 2-phenoxy-indan-1-one derivatives using in vitro cell models.

2-Phenoxy-indan-1-one derivatives (PIOs) are a series of novel central-acting cholinesterase inhibitors for the treatment of Alzheimer's disease (AD). The adequate distribution of PIOs to the central nervous system (CNS) is essential for its effectiveness. However, articles related with their permeability in terms of CNS penetration across the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) have not been found. This study was undertaken to evaluate the in vitro BBB and BCSFB transport of PIOs using Madin-Darby canine kidney (MDCK), MDCK-MDR1 and Z310 cell line models. As a result, the transepithelial transport of PIOs did not differ between MDCK and MDCK-MDR1, and the result suggested that PIOs were not substrates for P-gp, which means that multidrug resistance (MDR) function would not affect PIOs absorption and brain distribution. High permeability of PIOs in Z310 was found and it suggested that PIOs had high brain uptake potential. The experiment also showed that PIOs had inhibitory effects on the MDR1-mediated transport of Rhodamine123 with an IC50 value of 40-54 µM. And we suggested that 5,6-dimethoxy-1-indanone might be the pharmacophoric moiety of PIOs that interacts with the binding site of P-gp.