Using Phylogenomic Data to Explore the Effects of Relaxed Clocks and Calibration Strategies on Divergence Time Estimation: Primates as a Test Case.

Primates have long been a test case for the development of phylogenetic methods for divergence time estimation. Despite a large number of studies, however, the timing of origination of crown Primates relative to the Cretaceous-Paleogene (K-Pg) boundary and the timing of diversification of the main crown groups remain controversial. Here, we analysed a data set of 372 taxa (367 Primates and 5 outgroups, 3.4 million aligned base pairs) that includes nine primate genomes. We systematically explore the effect of different interpretations of fossil calibrations and molecular clock models on primate divergence time estimates. We find that even small differences in the construction of fossil calibrations can have a noticeable impact on estimated divergence times, especially for the oldest nodes in the tree. Notably, choice of molecular rate model (autocorrelated or independently distributed rates) has an especially strong effect on estimated times, with the independent rates model producing considerably more ancient age estimates for the deeper nodes in the phylogeny. We implement thermodynamic integration, combined with Gaussian quadrature, in the program MCMCTree, and use it to calculate Bayes factors for clock models. Bayesian model selection indicates that the autocorrelated rates model fits the primate data substantially better, and we conclude that time estimates under this model should be preferred. We show that for eight core nodes in the phylogeny, uncertainty in time estimates is close to the theoretical limit imposed by fossil uncertainties. Thus, these estimates are unlikely to be improved by collecting additional molecular sequence data. All analyses place the origin of Primates close to the K-Pg boundary, either in the Cretaceous or straddling the boundary into the Palaeogene

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

A novel family of diversified immunoregulatory receptors in teleosts is homologous to both mammalian Fc receptors and molecules encoded within the leukocyte receptor complex

Three novel and closely related leukocyte immune-type receptors (IpLITR) have been identified in channel catfish (Ictalurus punctatus). These receptors belong to a large polymorphic and polygenic subset of the Ig superfamily with members located on at least three independently segregating loci. Like mammalian and avian innate immune regulatory receptors, IpLITRs have both putative inhibitory and stimulatory forms, with multiple types coexpressed in various lymphoid tissues and clonal leukocyte cell lines. IpLITRs have an unusual and novel relationship to mammalian and avian innate immune receptors: the membrane distal Ig domains of an individual IpLITR are related to fragment crystallizable receptors (FcRs) and FcR-like proteins, whereas the membrane proximal Ig domains are related to several leukocyte receptor complex encoded receptors. This unique composition of Ig domains within individual receptors supports the hypothesis that functionally and genomically distinct immune receptor families found in tetrapods may have evolved from such ancestral genes by duplication and recombination events. Furthermore, the discovery of a large heterogeneous family of immunoregulatory receptors in teleosts, reminiscent of amphibian, avian, and mammalian Ig-like receptors, suggests that complex innate immune receptor networks have been conserved during vertebrate evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00251-006-0134-1 and is accessible for authorized users

Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs.

The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. The same developmental origin makes it difficult to identify specific markers that discern between an intraembryonic versus YS-origin using a lineage trace approach. Additionally, the highly migratory nature of blood cells and the inability of pre-circulatory embryonic cells (i.e., 5-7 somite pairs (sp)) to robustly engraft in transplantation, even after culture, has precluded scientists from properly answering these questions. Here we report robust, multi-lineage and serially transplantable dHSC activity from cultured 2-7sp murine embryonic explants (Em-Ex). dHSC are undetectable in 2-7sp YS explants. Additionally, the engraftment from Em-Ex is confined to an emerging CD31+CD45+c-Kit+CD41- population. In sum, our work supports a model in which the embryo, not the YS, is the major source of lifelong definitive hematopoiesis

Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis

Citation: Hanzlicek, G. A., Raghavan, R. K., Ganta, R. R., & Anderson, G. A. (2016). Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis. Plos One, 11(3), 13. doi:10.1371/journal.pone.0151924The space-time pattern and environmental drivers (land cover, climate) of bovine anaplasmosis in the Midwestern state of Kansas was retrospectively evaluated using Bayesian hierarchical spatio-temporal models and publicly available, remotely-sensed environmental covariate information. Cases of bovine anaplasmosis positively diagnosed at Kansas State Veterinary Diagnostic Laboratory (n = 478) between years 2005-2013 were used to construct the models, which included random effects for space, time and space-time interaction effects with defined priors, and fixed-effect covariates selected a priori using an univariate screening procedure. The Bayesian posterior median and 95% credible intervals for the space-time interaction term in the best-fitting covariate model indicated a steady progression of bovine anaplasmosis over time and geographic area in the state. Posterior median estimates and 95% credible intervals derived for covariates in the final covariate model indicated land surface temperature (minimum), relative humidity and diurnal temperature range to be important risk factors for bovine anaplasmosis in the study. The model performance measured using the Area Under the Curve (AUC) value indicated a good performance for the covariate model (>0.7). The relevance of climatological factors for bovine anaplasmosis is discussed

Individual and Situational Factors Related to Young Women’s Likelihood of Confronting Sexism in Their Everyday Lives

Factors related to young women’s reported likelihood of confronting sexism were investigated. Participants were 338 U.S. female undergraduates (M = 19 years) attending a California university. They were asked to complete questionnaire measures and to write a personal narrative about an experience with sexism. Approximately half (46%) the women reported confronting the perpetrator. Individual factors (prior experience with sexism, feminist identification, collective action) and situational factors (familiarity and status of perpetrator, type of sexism) were tested as predictors in a logistic regression. Women were less likely to report confronting sexism if (1) they did not identify as feminists, (2) the perpetrator was unfamiliar or high-status/familiar (vs. familiar/equal-status), or (3) the type of sexism involved unwanted sexual attention (vs. sexist comments)