MMP-15 Is Upregulated in Preeclampsia, but Does Not Cleave Endoglin to Produce Soluble Endoglin

Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15–phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity–also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03) up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8) compared to gestationally matched preterm controls (n = 8). However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin

Влияние фосфатных связующих на физико-механические свойства периклазохромитовых огнеупоров

У данній статті наведено та порівняно фізико-механічні властивості периклазо-хромітових матеріалів в залежності від різних типів фосфатних зв’язуючих та введення різних домішок. Визначено, що найбільш раціональним є введення триполіфосфату натрію.In given clause are resulted and the physycal-mechanical properties periclase-cgromite of materials are compared depending on different of types phosphate binding and introduction of the various additives. Is determined, that most rational is the introduction treepolyphosphate sodume

Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+

Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances

Test of lepton flavor universality by the measurement of the branching fraction using three-prong decays

The ratio of branching fractions R(D∗-)≡B(B0→D∗-τ+ντ)/B(B0→D∗-μ+νμ) is measured using a data sample of proton-proton collisions collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3 fb-1. The τ lepton is reconstructed with three charged pions in the final state. A novel method is used that exploits the different vertex topologies of signal and backgrounds to isolate samples of semitauonic decays of b hadrons with high purity. Using the B0→D∗-π+π-π+ decay as the normalization channel, the ratio B(B0→D∗-τ+ντ)/B(B0→D∗-π+π-π+) is measured to be 1.97±0.13±0.18, where the first uncertainty is statistical and the second systematic. An average of branching fraction measurements for the normalization channel is used to derive B(B0→D∗-τ+ντ)=(1.42±0.094±0.129±0.054)%, where the third uncertainty is due to the limited knowledge of B(B0→D∗-π+π-π+). A test of lepton flavor universality is performed using the well-measured branching fraction B(B0→D∗-μ+νμ) to compute R(D∗-)=0.291±0.019±0.026±0.013, where the third uncertainty originates from the uncertainties on B(B0→D∗-π+π-π+) and B(B0→D∗-μ+νμ). This measurement is in agreement with the Standard Model prediction and with previous measurements

Meausrement of CP observables in B-->DK*+ decays using two and four body D final states

Measurements of CP observables in B± → DK*± decays are presented, where D denotes a superposition of D0 and D0 meson states. Decays of the D meson to K- Π+, K-K+, Π-Π+, K- Π+ Π- Π+ and Π- Π+ Π- Π+ are used and the K*± meson is reconstructed in the K0 S± Π final state. This analysis uses a data sample of pp collisions collected with the LHCb experiment, corresponding to integrated luminosities of 1 fb-1, 2 fb-1 and 1.8 fb-1 at centre-of-mass energies p s = 7TeV, 8TeV and 13TeV, respectively. The sensitivity of the results to the CKM angle is discussed