Cholesterol lowering in diet-induced hypercholesterolemic mice using Lactobacillus bile salt hydrolases with different substrate specificities.

The cholesterol-lowering effect of lactic acid bacteria with high activity of bile salt hydrolase (BSH) is unclear. We believe that distinguishing BSH substrate specificity is necessary to study the effect of various BSH enzymes. We engineered a BSH mutant enzyme recombinant strain named F67A, which exclusively hydrolyzes taurocholic acid (TCA) using site-directed mutagenesis, and a previously lab-constructed BSH recombinant strain, YB81 that exclusively hydrolyzes glycocholic acid (GCA). We also constructed the recombinant strain named NB5462, which carries the empty pSIP411 plasmid and was used as a blank control strain. The intestinal flora in pseudo-germ-free (PGF) mice in which intestinal flora were eliminated via antibiotics, and F67A successfully reduced serum cholesterol levels in high-cholesterol diet-fed mice, whereas YB81 did not yield the same results. However, YB81 regained its cholesterol-lowering capacity in specific pathogen-free (SPF) mice with intact intestinal flora. The cholesterol-lowering mechanism of F67A involved modifying the bile acid pool through BSH enzyme activity. This adjustment regulated the expression of intestinal farnesoid X receptor and subsequently elevated hepatic cholesterol 7α-hydroxylase (CYP7A1), effectively reducing cholesterol levels. Conversely, GCA, the substrate of YB81, was found in minimal quantities in mice, preventing it from inducing changes in bile acid pools. In the presence of intestinal flora, the YB81 BSH enzyme induced notable alterations in bile acids by regulating changes in the intestinal flora and BSH within the flora, ultimately resulting in cholesterol reduction. This is the first study investigating the substrate specificity of BSH, demonstrating that different substrate-specific BSH enzymes exhibit cholesterol-lowering properties. Additionally, we elaborate on the mechanism of BSH-mediated enterohepatic axis regulation.

Geomagnetic secular variation forecast using the NASA GEMS ensemble Kalman filter: A candidate SV model for IGRF-13.

ABSTRACT: We have produced a 5-year mean secular variation (SV) of the geomagnetic field for the period 2020-2025. We use the NASA Geomagnetic Ensemble Modeling System (GEMS), which consists of the NASA Goddard geodynamo model and ensemble Kalman filter (EnKF) with 400 ensemble members. Geomagnetic field models are used as observations for the assimilation, including gufm1 (1590-1960), CM4 (1961-2000) and CM6 (2001-2019). The forecast involves a bias correction scheme that assumes that the model bias changes on timescales much longer than the forecast period, so that they can be removed by successive forecast series. The algorithm was validated on the time period 2010-2015 by comparing with CM6 before being applied to the 2020-2025 time period. This forecast has been submitted as a candidate predictive model of IGRF-13 for the period 2020-2025.

Geodetic evidence that Mercury has a solid inner core.

Geodetic analysis of radio tracking measurements of the MESSENGER spacecraft while in orbit about Mercury has yielded new estimates for the planet's gravity field, tidal Love number, and pole coordinates. The derived right ascension (α = 281.0082° ± 0.0009°; all uncertainties are 3 standard deviations) and declination (δ =61.4164° ± 0.0003°) of the spin pole place Mercury in the Cassini state. Confirmation of the equilibrium state with an estimated mean (whole-planet) obliquity ϵ of 1.968 ± 0.027 arcmin enables the confident determination of the planet's normalized polar moment of inertia (0.333 ± 0.005), which indicates a high degree of internal differentiation. Internal structure models generated by a Markov-Chain Monte Carlo process and consistent with the geodetic constraints possess a solid inner core with a radius (r ic ) between 0.3 and 0.7 that of the outer core (r oc ).

Assessment of the effect of three-dimensional mantle density heterogeneity on earth rotation in tidal frequencies.

In this paper we report the assessment of the effect of the three-dimensional (3D) density heterogeneity in the mantle on Earth Orientation Parameters (EOP) (i.e., the polar motion, or PM, and the length of day, or LOD) in the tidal frequencies. The 3D mantle density model is estimated based upon a global S-wave velocity tomography model (S16U6L8) and the mineralogical knowledge derived from laboratory experiment. The lateral density variation is referenced against the Preliminary Reference Earth Model (PREM). Using this approach the effects of the heterogeneous mantle density variation in all three tidal frequencies (zonal long periods, tesseral diurnal, and sectorial semidiurnal) are estimated in both PM and LOD. When compared with mass or density perturbations originated on the earth's surface such as the oceanic and barometric changes, the heterogeneous mantle only contributes less than 10% of the total variation in PM and LOD in tidal frequencies. Nevertheless, including the 3D variation of the density in the mantle into account explained a substantial portion of the discrepancy between the observed signals in PM and LOD extracted from the lump-sum values based on continuous space geodetic measurement campaigns (e.g., CONT94) and the computed contribution from ocean tides as predicted by tide models derived from satellite altimetry observations (e.g., TOPEX/Poseidon). In other word, the difference of the two, at all tidal frequencies (long-periods, diurnals, and semi-diurnals) contains contributions of the lateral density heterogeneity of the mantle. Study of the effect of mantle density heterogeneity effect on torque-free earth rotation may provide useful constraints to construct the Reference Earth Model (REM), which is the next major objective in global geophysics research beyond PREM.