Molecular phylogeny of brachiopods and phoronids based on nuclear-encoded small subunit ribosomal RNA gene sequences

Brachiopod and phoronid phylogeny is inferred from SSU rDNA sequences of 28 articulate and nine inarticulate brachiopods, three phoronids, two ectoprocts and various outgroups, using gene trees reconstructed by weighted parsimony, distance and maximum likelihood methods. Of these sequences, 33 from brachiopods, two from phoronids and one each from an ectoproct and a priapulan are newly determined. The brachiopod sequences belong to 31 different genera and thus survey about 10% of extant genus-level diversity. Sequences determined in different laboratories and those from closely related taxa agree well, but evidence is presented suggesting that one published phoronid sequence (GenBank accession UO12648) is a brachiopod-phoronid chimaera, and this sequence is excluded from the analyses. The chiton, Acanthopleura, is identified as the phenetically proximal outgroup; other selected outgroups were chosen to allow comparison with recent, non-molecular analyses of brachiopod phylogeny. The different outgroups and methods of phylogenetic reconstruction lead to similar results, with differences mainly in the resolution of weakly supported ancient and recent nodes, including the divergence of inarticulate brachiopod sub-phyla, the position of the rhynchonellids in relation to long- and short-looped articulate brachiopod clades and the relationships of some articulate brachiopod genera and species. Attention is drawn to the problem presented by nodes that are strongly supported by non-molecular evidence but receive only low bootstrap resampling support. Overall, the gene trees agree with morphology-based brachiopod taxonomy, but novel relationships are tentatively suggested for thecideidine and megathyrid brachiopods. Articulate brachiopods are found to be monophyletic in all reconstructions, but monophyly of inarticulate brachiopods and the possible inclusion of phoronids in the inarticulate brachiopod clade are less strongly established. Phoronids are clearly excluded from a sister-group relationship with articulate brachiopods, this proposed relationship being due to the rejected, chimaeric sequence (GenBank UO12648). Lineage relative rate tests show no heterogeneity of evolutionary rate among articulate brachiopod sequences, but indicate that inarticulate brachiopod plus phoronid sequences evolve somewhat more slowly. Both brachiopods and phoronids evolve slowly by comparison with other invertebrates. A number of palaeontologically dated times of earliest appearance are used to make upper and lower estimates of the global rate of brachiopod SSU rDNA evolution, and these estimates are used to infer the likely divergence times of other nodes in the gene tree. There is reasonable agreement between most inferred molecular and palaeontological ages. The estimated rates of SSU rDNA sequence evolution suggest that the last common ancestor of brachiopods, chitons and other protostome invertebrates (Lophotrochozoa and Ecdysozoa) lived deep in Precambrian time. Results of this first DNA-based, taxonomically representative analysis of brachiopod phylogeny are in broad agreement with current morphology-based classification and systematics and are largely consistent with the hypothesis that brachiopod shell ontogeny and morphology are a good guide to phylogeny

Atypical B cells (CD21-CD27-IgD-) correlate with lack of response to checkpoint inhibitor therapy in NSCLC

Introduction: Checkpoint inhibitor (CI) therapy has revolutionized treatment for non-small cell lung cancer (NSCLC). However, a proportion of patients do not respond to CI therapy for unknown reasons. Although the current paradigm in anti-tumor immunity evolves around T cells, the presence of tertiary lymphoid structures and memory B cells has been positively correlated with response to CI therapy in NSCLC. In addition, double negative (DN) (CD27- IgD-) B cells have been shown to be abundant in NSCLC compared to healthy lung tissue and inversely correlate with the intratumoral presence of memory B cells. Nonetheless, no study has correlated DN B cells to survival in NSCLC. Methods: In this study, we evaluated the presence and phenotype of B cells in peripheral blood with flow cytometry of patients with NSCLC and mesothelioma before receiving CI therapy and correlated these with clinical outcome. Results: Non-responding patients showed decreased frequencies of B cells, yet increased frequencies of antigen-experienced CD21- DN (Atypical) B cells compared to responding patients and HC, which was confirmed in patients with mesothelioma treated with CI therapy. Conclusions: These data show that the frequency of CD21- DN B cells correlates with lack of response to CI therapy in thoracic malignancies. The mechanism by which CD21- DN B cells hamper CI therapy remains unknown. Our findings support the hypothesis that CD21- DN B cells resemble phenotypically identical exhausted B cells that are seen in chronic infection or function as antigen presenting cells that induce regulatory T cells.</p

Properties of 3-manifolds for relativists

In canonical quantum gravity certain topological properties of 3-manifolds are of interest. This article gives an account of those properties which have so far received sufficient attention, especially those concerning the diffeomorphism groups of 3-manifolds. We give a summary of these properties and list some old and new results concerning them. The appendix contains a discussion of the group of large diffeomorphisms of the $l$-handle 3-manifold.Comment: 20 pages. Plain-TeX, no figures, 1 Table (A4 format

Homotopy types of stabilizers and orbits of Morse functions on surfaces

Let $M$ be a smooth compact surface, orientable or not, with boundary or without it, $P$ either the real line $R^1$ or the circle $S^1$, and $Diff(M)$ the group of diffeomorphisms of $M$ acting on $C^{\infty}(M,P)$ by the rule $h\cdot f\mapsto f \circ h^{-1}$, where $h\in Diff(M)$ and $f \in C^{\infty}(M,P)$. Let $f:M \to P$ be a Morse function and $O(f)$ be the orbit of $f$ under this action. We prove that $\pi_k O(f)=\pi_k M$ for $k\geq 3$, and $\pi_2 O(f)=0$ except for few cases. In particular, $O(f)$ is aspherical, provided so is $M$. Moreover, $\pi_1 O(f)$ is an extension of a finitely generated free abelian group with a (finite) subgroup of the group of automorphisms of the Reeb graph of $f$. We also give a complete proof of the fact that the orbit $O(f)$ is tame Frechet submanifold of $C^{\infty}(M,P)$ of finite codimension, and that the projection $Diff(M) \to O(f)$ is a principal locally trivial $S(f)$-fibration.Comment: 49 pages, 8 figures. This version includes the proof of the fact that the orbits of a finite codimension of tame action of tame Lie group on tame Frechet manifold is a tame Frechet manifold itsel

PTPRR (protein tyrosine phosphatase, receptor type, R)

Review on PTPRR (protein tyrosine phosphatase, receptor type, R), with data on DNA, on the protein encoded, and where the gene is implicated

Structural plasticity of the selectivity filter in a nonselective ion channel

The sodium potassium ion channel (NaK) is a nonselective ion channel that conducts both sodium and potassium across the cellular membrane. A new crystallographic structure of NaK reveals conformational differences in the residues that make up the selectivity filter between the four subunits that form the ion channel and the inner helix of the ion channel. The crystallographic structure also identifies a side-entry, ion-conduction pathway for Na+ permeation that is unique to NaK. NMR studies and molecular dynamics simulations confirmed the dynamical nature of the top part of the selectivity filter and the inner helix in NaK as also observed in the crystal structure. Taken together, these results indicate that the structural plasticity of the selectivity filter combined with the dynamics of the inner helix of NaK are vital for the efficient conduction of different ions through the non-selective ion channel of NaK

Kinetic Anomalies in Addition-Aggregation Processes

We investigate irreversible aggregation in which monomer-monomer, monomer-cluster, and cluster-cluster reactions occur with constant but distinct rates K_{MM}, K_{MC}, and K_{CC}, respectively. The dynamics crucially depends on the ratio gamma=K_{CC}/K_{MC} and secondarily on epsilon=K_{MM}/K_{MC}. For epsilon=0 and gamma<2, there is conventional scaling in the long-time limit, with a single mass scale that grows linearly in time. For gamma >= 2, there is unusual behavior in which the concentration of clusters of mass k, c_k decays as a stretched exponential in time within a boundary layer k<k* propto t^{1-2/gamma} (k* propto ln t for gamma=2), while c_k propto t^{-2} in the bulk region k>k*. When epsilon>0, analogous behaviors emerge for gamma<2 and gamma >= 2.Comment: 6 pages, 2 column revtex4 format, for submission to J. Phys.

Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients

Tacrolimus is the backbone of immunosuppressive agents to prevent transplant rejection. Paradoxically, tacrolimus is nephrotoxic, causing irreversible tubulointerstitial damage. Therefore, infusion of mesenchymal stromal cells (MSC) 6 and 7 weeks post-transplantation was assessed to facilitate withdrawal of tacrolimus in the randomized phase II TRITON trial. Here, we performed detailed analysis of the peripheral blood immune composition using mass cytometry to assess potential effects of MSC therapy on the immune system. We developed two metal-conjugated antibody panels containing 40 antibodies each. PBMC samples from 21 MSC-treated patients and 13 controls, obtained pre-transplant and at 24 and 52 weeks post-transplantation, were analyzed. In the MSC group at 24 weeks, 17 CD4+ T cell clusters were increased of which 14 Th2-like clusters and three Th1/Th2-like clusters, as well as CD4+FoxP3+ Tregs. Additionally, five B cell clusters were increased, representing either class switched memory B cells or proliferating B cells. At 52 weeks, CCR7+CD38+ mature B cells were decreased. Finally, eight Tc1 (effector) memory cytotoxic T cell clusters were increased. Our work provides a comprehensive account of the peripheral blood immune cell composition in kidney transplant recipients after MSC therapy and tacrolimus withdrawal. These results may help improving therapeutic strategies using MSCs with the aim to reduce the use of calcineurin inhibitors. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02057965.</p