Direct Evidence for Specific Interactions of the Fibrinogen αC-Domains with the Central E Region and with Each Other †

The carboxyl-terminal regions of the fibrinogen Aα chains (αC regions) form compact αC-domains tethered to the bulk of the molecule with flexible αC-connectors. It was hypothesized that in fibrinogen two αC-domains interact intramolecularly with each other and with the central E region preferentially through its N-termini of Bβ chains, and that removal of fibrinopeptides A and B upon fibrin assembly results in dissociation of the αC regions and their switch to intermolecular interactions. To test this hypothesis, we studied the interactions of the recombinant αC region (Aα221-610 fragment) and its sub-fragments, αC-connector (Aα221-391) and αC-domain (Aα392-610), between each other and with the recombinant (Bβ1-66)2 and (β15-66)2 fragments and NDSK corresponding to the fibrin(ogen) central E region, using laser tweezers-based force spectroscopy. TheαC-domain, but not the αC-connector, bound to NDSK, which contains fibrinopeptides A and B, and less frequently to desA-NDSK and (Bβ1-66)2 containing only fibrinopeptides B; it was poorly reactive with desAB-NDSK and (β15-66)2 both lacking fibrinopeptides B. The interactions of the αC-domains with each other and with the αC-connector were also observed, although they were weaker and heterogeneous in strength. These results provide the first direct evidence for the interaction between the αC-domains and the central E region through fibrinopeptides B, in agreement with the above hypothesis, and indicate that fibrinopeptides A are also involved. They also confirm the hypothesized homomeric interactions between the αC-domains and display their interaction with the αC-connectors, which may contribute to covalent cross-linking of α polymers in fibrin

The Interaction of Integrin α IIb β 3 with Fibrin Occurs through Multiple Binding Sites in the α IIb β-Propeller Domain

The currently available antithrombotic agents target the interaction of platelet integrin αIIbβ3 (GPIIb-IIIa) with fibrinogen during platelet aggregation. Platelets also bind fibrin formed early during thrombus growth. It was proposed that inhibition of platelet-fibrin interactions may be a necessary and important property of αIIbβ3 antagonists; however, the mechanisms by which αIIbβ3 binds fibrin are uncertain. We have previously identified the γ370–381 sequence (P3) in the γC domain of fibrinogen as the fibrin-specific binding site for αIIbβ3 involved in platelet adhesion and platelet-mediated fibrin clot retraction. In the present study, we have demonstrated that P3 can bind to several discontinuous segments within the αIIb β-propeller domain of αIIbβ3 enriched with negatively charged and aromatic residues. By screening peptide libraries spanning the sequence of the αIIb β-propeller, several sequences were identified as candidate contact sites for P3. Synthetic peptides duplicating these segments inhibited platelet adhesion and clot retraction but not platelet aggregation, supporting the role of these regions in fibrin recognition. Mutant αIIbβ3 receptors in which residues identified as critical for P3 binding were substituted for homologous residues in the I-less integrin αMβ2 exhibited reduced cell adhesion and clot retraction. These residues are different from those that are involved in the coordination of the fibrinogen γ404–411 sequence and from auxiliary sites implicated in binding of soluble fibrinogen. These results map the binding of fibrin to multiple sites in the αIIb β-propeller and further indicate that recognition specificity of αIIbβ3 for fibrin differs from that for soluble fibrinogen

Thermal structure and cooling of superfluid neutron stars with accreted magnetized envelopes

We study the thermal structure of neutron stars with magnetized envelopes composed of accreted material, using updated thermal conductivities of plasmas in quantizing magnetic fields, as well as equation of state and radiative opacities for partially ionized hydrogen in strong magnetic fields. The relation between the internal and local surface temperatures is calculated and fitted by an analytic function of the internal temperature, magnetic field strength, angle between the field lines and the normal to the surface, surface gravity, and the mass of the accreted material. The luminosity of a neutron star with a dipole magnetic field is calculated for various values of the accreted mass, internal temperature, and magnetic field strength. Using these results, we simulate cooling of superfluid neutron stars with magnetized accreted envelopes. We consider slow and fast cooling regimes, paying special attention to very slow cooling of low-mass superfluid neutron stars. In the latter case, the cooling is strongly affected by the combined effect of magnetized accreted envelopes and neutron superfluidity in the stellar crust. Our results are important for interpretation of observations of isolated neutron stars hottest for their age, such as RX J0822-43 and PSR B1055-52.Comment: 15 pages, 12 figures, 2 tables. Corrected title only (v2

Top quark mass definition and top quark pair production near threshold at the NLC

We suggest an infrared-insensitive quark mass, defined by subtracting the soft part of the quark self energy from the pole mass. We demonstrate the deep relation of this definition with the static quark-antiquark potential. At leading order in 1/m this mass coincides with the PS mass which is defined in a completely different manner. Going beyond static limit, the small normalization point introduces recoil corrections which are calculated here as well. Using this mass concept and other concepts for the quark mass we calculate the cross section of e+ e- -> t t-bar near threshold at NNLO accuracy adopting three alternative approaches, namely (1) fixing the pole mass, (2) fixing the PS mass, and (3) fixing the new mass which we call the PS-bar mass. We demonstrate that perturbative predictions for the cross section become much more stable if we use the PS or the PS-bar mass for the calculations. A careful analysis suggests that the top quark mass can be extracted from a threshold scan at NLC with an accuracy of about 100-200 MeV.Comment: published version, 21 pages in LaTeX including 11 PostScript figure

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

A new species of Dyspessa Hübner, (Lepidoptera, Cossidae) from Western China, with catalogue of Chinese species of the genus

Yakovlev, Roman V., Saldaitis, Aidas, Pekarsky, Oleg (2016): A new species of Dyspessa Hübner, (Lepidoptera, Cossidae) from Western China, with catalogue of Chinese species of the genus. Zootaxa 4107 (1): 85-88, DOI: http://doi.org/10.11646/zootaxa.4107.1.