The solution structure of heparan sulfate differs from that of heparin: implications for function.

The highly sulfated polysaccharides heparin and heparan sulfate (HS) play key roles in the regulation of physiological and pathophysiological processes. Despite its importance, no molecular structures of free HS have been reported up to now. By combining analytical ultracentrifugation, small-angle X-ray scattering and constrained scattering modelling recently used for heparin, we have analysed the solution structures for eight purified HS fragments dp6 to dp24 corresponding to the predominantly unsulfated GlcA-GlcNAc domains of heparan sulfate. Unlike heparin, the sedimentation coefficient s20,w of HS dp6-dp24 showed a small rotor speed dependence, where similar s20,w values of 0.82 to 1.26 S (absorbance optics) and 1.05 to 1.34 S (interference optics) were determined. The corresponding X-ray scattering measurements of HS dp6-dp24 gave radii of gyration RG values from 1.03 nm to 2.82 nm, cross-sectional radii of gyration RXS values from 0.31 nm to 0.65 nm, and maximum lengths L from 3.0 nm to 10.0 nm. These data showed that HS has a longer and more bent structure than heparin. Constrained scattering modelling starting from 5,000-12,000 conformationally-randomised HS structures gave best fit dp6-dp24 molecular structures that were longer and more bent than their equivalents in heparin. Alternative fits were obtained for HS dp18 and dp24, indicating their higher bending and flexibility. We conclude that HS displays bent conformations that are significantly distinct from that for heparin. The difference is attributed to the different predominant monosaccharide sequence and reduced sulphation of HS, indicating that HS may interact differently with proteins compared to heparin

Vortices and Superfluidity in a Strongly Interacting Fermi Gas

Quantum-degenerate Fermi gases provide a remarkable opportunity to study strongly interacting fermions. In contrast to other Fermi systems, such as superconductors, neutron stars or the quark-gluon plasma, these gases have low densities and their interactions can be precisely controlled over an enormous range. Here we report observations of vortices in such a gas that provide definitive evidence for superfluidity. By varying the pairing strength between two fermions near a Feshbach resonance, one can explore the crossover from a Bose-Einstein condensate (BEC) of molecules to a Bardeen-Cooper-Schrieffer (BCS) superfluid of loosely bound pairs whose size is comparable to, or even larger than, the interparticle spacing. The crossover realizes a novel form of high-T_C superfluidity and it may provide new insight for high-T_C superconductors. Previous experiments with Fermi gases have revealed condensation of fermion pairs. While these and other studies were consistent with predictions assuming superfluidity, the smoking gun for superfluid behavior has been elusive. Our observation of vortex lattices directly displays superfluid flow in a strongly interacting, rotating Fermi gas.Comment: 14 pages, including 7 figures, submitted to Natur

In situ size sorting in CVD synthesis of Si microspheres

[EN] Silicon microspheres produced in gas-phase by hot-wall CVD offer unique quality in terms of sphericity, surface smoothness, and size. However, the spheres produced are polydisperse in size, which typically range from 0.5 mu m to 5 mu m. In this work we show through experiments and calculations that thermophoretic forces arising from strong temperature gradients inside the reactor volume effectively sort the particles in size along the reactor. These temperature gradients are shown to be produced by a convective gas flow. The results prove that it is possible to select the particle size by collecting them in a particular reactor region, opening new possibilities towards the production by CVD of size-controlled high-quality silicon microspheres.The authors acknowledge financial support from the following projects: ENE2013-49984-EXP, MAT2012-35040, MAT2015-69669-P and ESP2014-54256-C4-2-R of the Spanish Ministry of Economy and Competitiveness (MINECO), and PROMETEOII/2014/026 of the Regional Valencian Government.Garín Escrivá, M.; Fenollosa Esteve, R.; Kowalski, L. (2016). In situ size sorting in CVD synthesis of Si microspheres. Scientific Reports. 6:1-10. https://doi.org/10.1038/srep38719S110

Tracing Functional Antigen-Specific CCR6+ Th17 Cells after Vaccination

BACKGROUND: The function of T helper cell subsets in vivo depends on their location, and one hallmark of T cell differentiation is the sequential regulation of migration-inducing chemokine receptor expression. CC-chemokine receptor 6 (CCR6) is a trait of tissue-homing effector T cells and has recently been described as a receptor on T helper type 17 (Th17) cells. Th17 cells are associated with autoimmunity and the defence against certain infections. Although, the polarization of Th cells into Th17 cells has been studied extensively in vitro, the development of those cells during the physiological immune response is still elusive. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the development and functionality of Th17 cells in immune-competent mice during an ongoing immune response. In naïve and vaccinated animals CCR6(+) Th cells produce IL-17. The robust homeostatic proliferation and the presence of activation markers on CCR6(+) Th cells indicate their activated status. Vaccination induces antigen-specific CCR6(+) Th17 cells that respond to in vitro re-stimulation with cytokine production and proliferation. Furthermore, depletion of CCR6(+) Th cells from donor leukocytes prevents recipients from severe disease in experimental autoimmune encephalomyelitis, a model for multiple sclerosis in mice. CONCLUSIONS/SIGNIFICANCE: In conclusion, we defined CCR6 as a specific marker for functional antigen-specific Th17 cells during the immune response. Since IL-17 production reaches the highest levels during the immediate early phase of the immune response and the activation of Th17 cells precedes the Th1 cell differentiation we tent to speculate that this particular Th cell subset may represent a first line effector Th cell subpopulation. Interference with the activation of this Th cell subtype provides an interesting strategy to prevent autoimmunity as well as to establish protective immunity against infections

Gene therapy for carcinoma of the breast: Genetic toxins

Gene therapy was initially envisaged as a potential treatment for genetically inherited, monogenic disorders. The applications of gene therapy have now become wider, however, and include cardiovascular diseases, vaccination and cancers in which conventional therapies have failed. With regard to oncology, various gene therapy approaches have been developed. Among them, the use of genetic toxins to kill cancer cells selectively is emerging. Two different types of genetic toxins have been developed so far: the metabolic toxins and the dominant-negative class of toxins. This review describes these two different approaches, and discusses their potential applications in cancer gene therapy

Measurement of the Relative Branching Fraction of Υ(4S)\Upsilon(4S) to Charged and Neutral B-Meson Pairs

We analyze 9.7 x 10^6 B\bar{B}$ pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Y(4S) resonance. We measure the rates for B^0 -> J/psi K^{(*)0} and B^+ -> J/psi K^{(*)+} decays and use the world-average B-meson lifetime ratio to extract the relative widths f+-/f00 = Gamma(Y(4S) -> B+B-)/Gamma(Y(4S) -> B0\bar{B0}) = = 1.04 +/- 0.07(stat) +/- 0.04(syst). With the assumption that f+- + f00 = 1, we obtain f00 = 0.49 +/- 0.02(stat) +/- 0.01(syst) and f+- = 0.51 +/- 0.02(stat) +/- 0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Y(4S) resonance.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

First Observation of the Decays B0→D∗−ppˉπ+B^{0}\to D^{*-}p\bar{p}\pi^{+} and B^{0}\to D^{*-}p\bar{n}$

We report the first observation of exclusive decays of the type B to D^* N anti-N X, where N is a nucleon. Using a sample of 9.7 times 10^{6} B-Bbar pairs collected with the CLEO detector operating at the Cornell Electron Storage Ring, we measure the branching fractions B(B^0 \to D^{*-} proton antiproton \pi^+) = ({6.5}^{+1.3}_{-1.2} +- 1.0) \times 10^{-4} and B(B^0 \to D^{*-} proton antineutron) = ({14.5}^{+3.4}_{-3.0} +- 2.7) times 10^{-4}. Antineutrons are identified by their annihilation in the CsI electromagnetic calorimeter.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Study of the Decays B0 --> D(*)+D(*)-

The decays B0 --> D*+D*-, B0 --> D*+D- and B0 --> D+D- are studied in 9.7 million Y(4S) --> BBbar decays accumulated with the CLEO detector. We determine Br(B0 --> D*+D*-) = (9.9+4.2-3.3+-1.2)e-4 and limit Br(B0 --> D*+D-) < 6.3e-4 and Br(B0 --> D+D-) < 9.4e-4 at 90% confidence level (CL). We also perform the first angular analysis of the B0 --> D*+D*- decay and determine that the CP-even fraction of the final state is greater than 0.11 at 90% CL. Future measurements of the time dependence of these decays may be useful for the investigation of CP violation in neutral B meson decays.Comment: 21 pages, 5 figures, submitted to Phys. Rev.

A Search for B→τνB\to \tau\nu

We report results of a search for $B\to\tau\nu$ in a sample of 9.7 million charged $B$ meson decays. The search uses both $\pi\nu$ and $\ell\nu\bar\nu$ decay modes of the $\tau$, and demands exclusive reconstruction of the companion $\bar B$ decay to suppress background. We set an upper limit on the branching fraction ${\cal B}(B\to \tau\nu) < 8.4\times 10^{-4}$ at 90% confidence level. With slight modification to the analysis we also establish ${\cal B}(B^\pm\to K^\pm\nu\bar\nu) < 2.4\times 10^{-4}$ at 90% confidence level.Comment: 10 ages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Measurements of B --> D_s^{(*)+} D^{*(*)} Branching Fractions

This article describes improved measurements by CLEO of the $B^0 \to D_s^+ D^{*-}$ and $B^0 \to D_s^{*+} D^{*-}$ branching fractions, and first evidence for the decay $B^+ \to D_s^{(*)+} \bar{D}^{**0}$, where $\bar{D}^{**0}$ represents the sum of the $\bar{D}_1(2420)^0$, $\bar{D}_2^*(2460)^0$, and $\bar{D}_1(j=1/2)^0$ L=1 charm meson states. Also reported is the first measurement of the $D_s^{*+}$ polarization in the decay $B^0 \to D_s^{*+} D^{*-}$. A partial reconstruction technique, employing only the fully reconstructed $D_s^+$ and slow pion $\pi_s^-$ from the $D^{*-} \to \bar{D}^0 \pi^-_s$ decay, enhances sensitivity. The observed branching fractions are ${\mathcal B} (B^0 \to D_s^+ D^{*-}) = (1.10 \pm 0.18 \pm 0.10 \pm 0.28)$, ${\mathcal B} (B^0 \to D_s^{*+} D^{*-}) = (1.82 \pm 0.37 \pm 0.24 \pm 0.46)$, and ${\mathcal B} (B^+ \to D_s^{(*)+} \bar{D}^{**0}) = (2.73 \pm 0.78 \pm 0.48 \pm 0.68)$, where the first error is statistical, the second systematic, and the third is due to the uncertainty in the $D_s^+ \to \phi \pi^+$ branching fraction. The measured $D_s^{*+}$ longitudinal polarization, $\Gamma_L/\Gamma = (50.6 \pm 13.9 \pm 3.6)$, is consistent with the factorization prediction of 54%.Comment: 26 pages (LaTeX), 15 figures. To be submitted to PR