Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity

The coevolution of humans and infectious agents has exerted selective pressure on the immune system to control potentially lethal infections. Correspondingly, pathogens have evolved with various strategies to modulate and circumvent the host's innate and adaptive immune response. Schistosoma species are helminth parasites with genes that have been selected to modulate the host to tolerate chronic worm infections, often for decades, without overt morbidity. The modulation of immunity by schistosomes has been shown to prevent a range of immune-mediated diseases, including allergies and autoimmunity. Individual immune-modulating schistosome molecules have, therefore, therapeutic potential as selective manipulators of the immune system to prevent unrelated diseases. Here we show that S. mansoni eggs secrete a protein into host tissues that binds certain chemokines and inhibits their interaction with host chemokine receptors and their biological activity. The purified recombinant S. mansoni chemokine binding protein (smCKBP) suppressed inflammation in several disease models. smCKBP is unrelated to host proteins and is the first described chemokine binding protein encoded by a pathogenic human parasite and may have potential as an antiinflammatory agent

Aza-cibalackrot: turning on singlet fission through crystal engineering

Singlet fission is a photophysical process that provides a pathway for more efficient harvesting of solar energy in photovoltaic devices. The design of singlet fission candidates is non-trivial and requires careful optimization of two key criteria: (1) correct energetic alignment and (2) appropriate intermolecular coupling. Meanwhile, this optimization must not come at the cost of molecular stability or feasibility for device applications. Cibalackrot is a historic and stable organic dye which, although it has been suggested to have ideal energetics, does not undergo singlet fission due to large interchromophore distances, as suggested by single crystal analysis. Thus, while the energetic alignment is satisfactory, the molecule does not have the desired intermolecular coupling. Herein, we improve this characteristic through molecular engineering with the first synthesis of an aza-cibalackrot and show, using ultrafast transient spectroscopy, that singlet fission is successfully "turned on.

Search for the 1/2+ intruder state in P 35

The excitation energy of deformed intruder states (specifically the 2p2h bandhead) as a function of proton number Z along N=20 is of interest both in terms of better understanding the evolution of nuclear structure between spherical Ca40 and the Island of Inversion nuclei, and for benchmarking theoretical descriptions in this region. At the center of the N=20 Island of Inversion, the npnh (where n=2,4,6) neutron excitations across a diminished N=20 gap result in deformed and collective ground states, as observed in Mg32. In heavier isotones, npnh excitations do not dominate in the ground states but are present in the relatively low-lying level schemes. With the aim of identifying the expected 2p2h - s1/2+ state in P35, the only N=20 isotone for which the neutron 2p2h excitation bandhead has not yet been identified, the S36(d,He3)P35 reaction has been revisited in inverse kinematics with the HELical Orbit Spectrometer (HELIOS) at the Argonne Tandem Linac Accelerator System (ATLAS). While a candidate state has not been located, an upper limit for the transfer reaction cross section to populate such a configuration within a 2.5 to 3.6 MeV energy range provides a stringent constraint on the wave function compositions in both S36 and P35

Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine

Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01B-adjuvanted RH5.1 malaria antigen — substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells

Lifetime measurement in excited and yrast superdeformed bands in Hg194

Nuclear level lifetimes have been measured in two superdeformed bands in Hg194 using the Doppler-shift attenuation method. Average transition quadrupole moments derived from the lifetimes of an excited and yrast superdeformed bands are Qt=17.6(30) and 17.2(20)eb, respectively. The Doppler shifts of the excited band relative to the yrast band indicate a slight difference in quadrupole moments [+4(5)%], assuming similar side feeding..ul2 These results imply that the second well is stable and rigid with respect to the particle excitation responsible for this excited band

Identification of the unfavored N=7 superdeformed band in Hg191

A new superdeformed band has been identified in Hg191 bringing the total number of bands observed in this nucleus to four. The new band has properties similar to those of a superdeformed band reported recently in Hg193. Both bands are believed to be built on the unfavored signature of the j15/2 intruder configuration. Comparisons between the data and cranked Woods-Saxon calculations highlight the strengths and weaknesses of theory in describing high-N orbitals at large deformation

New features of superdeformed bands in Hg194

Two new features of superdeformed (SD) bands in the A190 region emerge from a study of Hg194 with the Gammasphere detector array. A decrease of the dynamic moment of inertia is observed for rotational frequencies Latin small letter h with strokeω0.4 MeV, confirming long standing expectations based on mean field calculations with pairing. Evidence for a small staggering in the SD transition energies is also observed, suggesting the presence of terms with fourfold symmetry in the SD Hamiltonian

Onset of collectivity in neutron deficient Po196,198

We have studied via in-beam -ray spectroscopy Po196 and Po198, which are the first neutron-deficient Po isotopes to exhibit a collective low-lying structure. The ratios of yrast state energies and the E2 branching ratios of transitions from non-yrast to yrast states are indicative of a low-lying vibrational structure. The onset of collective motion in these isotopes can be attributed to the opening of the neutron i13/2 orbital at N112 and the resulting large overlap between the two valence protons in the h9/2 orbital and the valence neutrons in the i13/2 orbital