Interactions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis.

Lymphatic growth (lymphangiogenesis) within lymph nodes functions to promote dendritic cell entry and effector lymphocyte egress in response to infection or inflammation. Here we demonstrate a crucial role for lymphotoxin-beta receptor (LTβR) signaling to fibroblastic reticular cells (FRCs) by lymphotoxin-expressing B cells in driving mesenteric lymph node lymphangiogenesis following helminth infection. LTβR ligation on fibroblastic reticular cells leads to the production of B-cell-activating factor (BAFF), which synergized with interleukin-4 (IL-4) to promote the production of the lymphangiogenic factors, vascular endothelial growth factors (VEGF)-A and VEGF-C, by B cells. In addition, the BAFF-IL-4 synergy augments expression of lymphotoxin by antigen-activated B cells, promoting further B cell-fibroblastic reticular cell interactions. These results underlie the importance of lymphotoxin-dependent B cell-FRC cross talk in driving the expansion of lymphatic networks that function to promote and maintain immune responsiveness.The growth of lymph nodes in response to infection requires lymphangiogenesis. Dubey et al. show that the mesenteric lymph node lymphangiogenesis upon helminth infection depends on the signaling loop between the B and fibroblastic reticular cells (FRCs), whereby the FRCs respond to lymphotoxin secreted by B cells by releasing B cell activating factor

IL-4Rα-Expressing B Cells Are Required for CXCL13 Production by Fibroblastic Reticular Cells.

Adaptive type 2 immune responses against the intestinal helminth Heligmosomoides polygyrus (Hp) require the interaction of follicle-associated CXCR5 <sup>+</sup> dendritic cells with naive T cells in the draining mesenteric lymph nodes (mLNs). However, the source of CXCL13 responsible for attracting CXCR5 <sup>+</sup> dendritic cells has remained unclear. Using multiplex imaging combined with deep tissue analysis, we observed new CXCL13 <sup>+</sup> fibroblastic reticular cells surrounding paracortical and cortical B cell follicles in the mLNs of infected mice. CXCL13 <sup>+</sup> fibroblasts expressed markers of marginal reticular cells (MRCs), and their expansion required lymphotoxin (LT)-dependent interactions between IL-4Rα-expressing B cells and CCL19 <sup>+</sup> fibroblasts. Infection-induced follicles did not necessarily contain follicular dendritic cells (FDCs), indicating that CXCL13 <sup>+</sup> fibroblasts may instead drive their formation. These data reveal a role for lymphotoxin signaling to CCL19 <sup>+</sup> fibroblasts in the development of CXCL13 <sup>+</sup> MRC-like cells and adaptive type 2 immunity in response to helminth infection

Immune Antibodies and Helminth Products Drive CXCR2-Dependent Macrophage-Myofibroblast Crosstalk to Promote Intestinal Repair.

Helminth parasites can cause considerable damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination particularly during enteric infection. However, how protective type 2 responses targeted against these tissue-disruptive multicellular parasites might contribute to homeostatic wound healing in the intestine has remained unclear. Here, we observed that mice lacking antibodies (Aid-/-) or activating Fc receptors (Fcrg-/-) displayed impaired intestinal repair following infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb), whilst transfer of immune serum could partially restore chemokine production and rescue wound healing in Aid-/- mice. Impaired healing was associated with a reduced expression of CXCR2 ligands (CXCL2/3) by macrophages (MΦ) and myofibroblasts (MF) within intestinal lesions. Whilst antibodies and helminths together triggered CXCL2 production by MΦ in vitro via surface FcR engagement, chemokine secretion by intestinal MF was elicited by helminths directly via Fcrg-chain/dectin2 signaling. Blockade of CXCR2 during Hpb challenge infection reproduced the delayed wound repair observed in helminth infected Aid-/- and Fcrg-/- mice. Finally, conditioned media from human MΦ stimulated with infective larvae of the helminth Ascaris suum together with immune serum, promoted CXCR2-dependent scratch wound closure by human MF in vitro. Collectively our findings suggest that helminths and antibodies instruct a chemokine driven MΦ-MF crosstalk to promote intestinal repair, a capacity that may be harnessed in clinical settings of impaired wound healing

Data Mining Approaches to Diffuse Large B–Cell Lymphoma Gene Expression Data Interpretation

This paper presents a comprehensive study of gene expression patterns originating from a diffuse large B–cell lymphoma (DLBCL) database. It focuses on the implementation of feature selection and classification techniques. Thus, it firstly tackles the identification of relevant genes for the prediction of DLBCL types. It also allows the determination of key biomarkers to differentiate two subtypes of DLBCL samples: Activated B–Like and Germinal Centre B–Like DLBCL. Decision trees provide knowledge–based models to predict types and subtypes of DLBCL. This research suggests that the data may be insufficient to accurately predict DLBCL types or even detect functionally relevant genes. However, these methods represent reliable and understandable tools to start thinking about possible interesting non–linear interdependencies

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease ( 65 10 cm), thrombocytopenia (< 150 7 109/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

Measurement of the parity-violating longitudinal single-spin asymmetry for W±W^{\pm} boson production in polarized proton-proton collisions at s=500\sqrt{s} = 500 GeV

We report the first measurement of the parity violating single-spin asymmetries for midrapidity decay positrons and electrons from $W^{+}$ and $W^{-}$ boson production in longitudinally polarized proton-proton collisions at $\sqrt{s}=500$GeV by the STAR experiment at RHIC. The measured asymmetries, $A^{W^+}_{L}=-0.27\pm 0.10\;({\rm stat.})\pm 0.02\;({\rm syst.}) \pm 0.03\;({\rm norm.})$ and $A^{W^-}_{L}=0.14\pm 0.19\;({\rm stat.})\pm 0.02 \;({\rm syst.})\pm 0.01\;({\rm norm.})$, are consistent with theory predictions, which are large and of opposite sign. These predictions are based on polarized quark and antiquark distribution functions constrained by polarized DIS measurements.Comment: 6 pages, 4 figures, submitted to Physics Review Letter

Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at $\sqrt{s_{NN}} = 200$ GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, $\eta/s$, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of $\eta/s$ that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.

High pTp_{T} non-photonic electron production in pp+pp collisions at s\sqrt{s} = 200 GeV

We present the measurement of non-photonic electron production at high transverse momentum ($p_T >$ 2.5 GeV/$c$) in $p$ + $p$ collisions at $\sqrt{s}$ = 200 GeV using data recorded during 2005 and 2008 by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The measured cross-sections from the two runs are consistent with each other despite a large difference in photonic background levels due to different detector configurations. We compare the measured non-photonic electron cross-sections with previously published RHIC data and pQCD calculations. Using the relative contributions of B and D mesons to non-photonic electrons, we determine the integrated cross sections of electrons ($\frac{e^++e^-}{2}$) at 3 GeV/$c < p_T <~$10 GeV/$c$ from bottom and charm meson decays to be ${d\sigma_{(B\to e)+(B\to D \to e)} \over dy_e}|_{y_e=0}$ = 4.0$\pm0.5$({\rm stat.})$\pm1.1$({\rm syst.}) nb and ${d\sigma_{D\to e} \over dy_e}|_{y_e=0}$ = 6.2$\pm0.7$({\rm stat.})$\pm1.5$({\rm syst.}) nb, respectively.Comment: 17 pages, 17 figure