Cdc5-Dependent Asymmetric Localization of Bfa1 Fine-Tunes Timely Mitotic Exit

In budding yeast, the major regulator of the mitotic exit network (MEN) is Tem1, a GTPase, which is inhibited by the GTPase-activating protein (GAP), Bfa1/Bub2. Asymmetric Bfa1 localization to the bud-directed spindle pole body (SPB) during metaphase also controls mitotic exit, but the molecular mechanism and function of this localization are not well understood, particularly in unperturbed cells. We identified four novel Cdc5 target residues within the Bfa1 C-terminus: 452S, 453S, 454S, and 559S. A Bfa1 mutant in which all of these residues had been changed to alanine (Bfa14A) persisted on both SPBs at anaphase and was hypo-phosphorylated, despite retaining its GAP activity for Tem1. A Bfa1 phospho-mimetic mutant in which all of these residues were switched to aspartate (Bfa14D) always localized asymmetrically to the SPB. These observations demonstrate that asymmetric localization of Bfa1 is tightly linked to its Cdc5-dependent phosphorylation, but not to its GAP activity. Consistent with this, in kinase-defective cdc5-2 cells Bfa1 was not phosphorylated and localized to both SPBs, whereas Bfa14D was asymmetrically localized. BFA14A cells progressed through anaphase normally but displayed delayed mitotic exit in unperturbed cell cycles, while BFA14D cells underwent mitotic exit with the same kinetics as wild-type cells. We suggest that Cdc5 induces the asymmetric distribution of Bfa1 to the bud-directed SPB independently of Bfa1 GAP activity at anaphase and that Bfa1 asymmetry fine-tunes the timing of MEN activation in unperturbed cell cycles

Finite-Time Consensus of Networked Multiagent Systems with Time-Varying Linear Control Protocols

Finite-time consensus problems for networked multiagent systems with first-order/second-order dynamics are investigated in this paper. The goal of this paper is to design local information based control protocols such that the systems achieve consensus at any preset time. In order to realize this objective, a class of linear feedback control protocols with time-varying gains is introduced. We prove that the multiagent systems under such kinds of time-varying control protocols can achieve consensus at the preset time if the undirected communication graph is connected. Numerical simulations are presented to illustrate the effectiveness of the obtained theoretic results

Monovalent Ion Condensation at the Electrified Liquid/Liquid Interface

X-ray reflectivity studies demonstrate the condensation of a monovalent ion at the electrified interface between electrolyte solutions of water and 1,2-dichloroethane. Predictions of the ion distributions by standard Poisson-Boltzmann (Gouy-Chapman) theory are inconsistent with these data at higher applied interfacial electric potentials. Calculations from a Poisson-Boltzmann equation that incorporates a non-monotonic ion-specific potential of mean force are in good agreement with the data.Comment: 4 pages, 4 figure

Studies Based on Preparation, Physical Characteristics, and Cellular Pharmacological Activities of Thin PLGA Film Loaded with Geniposide

In this primary study, thin polylactic-co-glycolic acid (PLGA) film loaded with geniposide was first prepared and demonstrated on both physical and pharmacological aspects for its potential application on drug-eluting vascular stents. Physical parameters of geniposide-loaded thin film, such as crystal structure, molecular spectral characteristics, and release behavior in the whole process were detected. From X-Ray diffraction, the characteristic peak of crystal geniposide disappeared on geniposide-loaded PLGA film (GLPF) after it formed, which meant there was no agglomeration phenomenon, as geniposide was distributed in the form of single molecule. According to scanning electron microscopy (SEM) figure, the GLPF was more flat and uniform with better compactness. It inferred that release behavior of geniposide at the early stage (0~15 d) was in the form of free diffusion. Carrier PLGA began to degrade 15 days later, so the residual geniposide was also dissolved. Cellular pharmacological effects of geniposide on endothelial cells (ECs) and smooth muscle cells (SMCs) were also demonstrated on GLPF. 5% and 10% (w/w) geniposide-loaded PLGA (60 : 40) membrane indicated its significant effect on ECs promotion and SMCs inhibition. All provided feasible evidences for the development of new geniposide-coating vascular stent using PLGA as carrier

Comparison of the Bouguer reduction approach for the satellite gravity data: Case study of the eastern Tibetan Plateau and its adjacent areas

Gravimetrijski satelitski podaci u širokoj su primjeni u geofizici u proučavanju dubokih struktura na regionalnoj i globalnoj razini. Ti podaci uključuju i gravitacijske anomalije slobodnog zraka, koje obično treba korigirati na Bouguer-ovu gravitacijsku anomaliju, radi praktične primjene. Metode Bouguer-ove redukcije mogu se podijeliti u dvije skupine ovisno o primijenjenom koordinatnom sustavu: 1. metoda sfernih koordinata (SBG) i 2. metoda kartezijevih koordinata; potonja se dalje dijeli na metode CEBG i CBG, koje uključuju, odnosno ne uključuju korekciju zbog zakrivljenosti Zemlje. U ovom su radu podaci o gravitacijskim anomalijama slobodnog zraka s Istočno-tibetanske visoravni i susjednih područja korišteni kao ulazni podaci za usporedbu triju metoda Bouguer-ove korekcije gravitacije: CBG, CEBG i SBG. Usporedba ove tri Bouguer-ove metode za gravitacijsku korekciju pokazala je da u istraživanom području učinak zakrivljenosti Zemlje na gravitaciju raste s povećanjem nadmorske visine. Cilj je bio shvatiti točnost inverzije za podatke dobivene različitim pristupima Bouguer-ovim anomalijama gravitacije. Raspodjele dubine Mohorovičićevog diskontinuiteta dobiveni su inverzijom Bouguer-ovih gravitacijskih anomalija dobivenih primjenom CBG, CEBG i SBG metoda, a aktivni seizmički profili korišteni su kao reference za usporedbu i ocjenu. Rezultati pokazuju da se dubine Mohorovičićevog diskontinuiteta dobivene SBG inverzijom bolje podudaraju s izmjerenim dubinama na seizmičkom profilu. Stoga se SBG metoda preporučuje kao najrealističniji pristup u postupku globalnih ili regionalnih istraživanja koja koriste gravimetrijske podatke.Satellite gravity data are widely used in the field of geophysics to study deep structures at the regional and global scales. These data comprise free-air gravity anomaly data, which usually need to be corrected to a Bouguer gravity anomaly for practical application. Bouguer reduction approaches can be divided into two methods based on the coordinate system: the spherical coordinates method (SBG) and the Cartesian coordinates method; the latter is further divided into the CEBG and CBG methods, which do and do not include the Earth’s curvature correction. In this paper, free-air gravity anomaly data from the eastern Tibetan Plateau and its adjacent areas were used as the basic data to compare the CBG, CEBG, and SBG Bouguer gravity correction methods. The comparison of these three Bouguer gravity correction methods shows that the effect of the Earth’s curvature on the gravitational effect increases with increasing elevation in the study area. We want to understand the inversion accuracy for the data obtained by different Bouguer gravity reduction approaches. The depth distributions of the Moho were obtained by the interface inversion of the Bouguer gravity anomalies obtained by the CBG, CEBG, and SBG, and active seismic profiles were used as references for comparison and evaluation. The results show that the depths of the Moho obtained by the SBG inversion are more consistent with the measured seismic profile depths. Therefore, the SBG method is recommended as the most realistic approach in the process of global or regional research employing gravity data

QMCPACK: Advances in the development, efficiency, and application of auxiliary field and real-space variational and diffusion Quantum Monte Carlo

We review recent advances in the capabilities of the open source ab initio Quantum Monte Carlo (QMC) package QMCPACK and the workflow tool Nexus used for greater efficiency and reproducibility. The auxiliary field QMC (AFQMC) implementation has been greatly expanded to include k-point symmetries, tensor-hypercontraction, and accelerated graphical processing unit (GPU) support. These scaling and memory reductions greatly increase the number of orbitals that can practically be included in AFQMC calculations, increasing accuracy. Advances in real space methods include techniques for accurate computation of band gaps and for systematically improving the nodal surface of ground state wavefunctions. Results of these calculations can be used to validate application of more approximate electronic structure methods including GW and density functional based techniques. To provide an improved foundation for these calculations we utilize a new set of correlation-consistent effective core potentials (pseudopotentials) that are more accurate than previous sets; these can also be applied in quantum-chemical and other many-body applications, not only QMC. These advances increase the efficiency, accuracy, and range of properties that can be studied in both molecules and materials with QMC and QMCPACK

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics

Background: Intrahepatic cholestasis (IC) is a disorder of bile production, secretion, and excretion with various causes. Crocin I (CR) is effective in the treatment of IC, but its underlying mechanisms need to be further explored. We aimed to reveal the therapeutic mechanism of crocin I for IC by combining an integrated strategy of metabolomics and transcriptomics.Methods: The hepatoprotective effect of CR against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) was evaluated in rats. The serum biochemical indices, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β), as well as the liver oxidative stress indexes and the pathological characteristics of the liver were analyzed. In addition, we also performed a serum metabolomics study using UPLC-Q Exactive HF-X technology to investigate the effect of CR on the serum of rats with ANIT-induced IC and screened potential biomarkers. The enrichment analysis of differential expressed genes (DEGs) was performed by transcriptomics. Finally, the regulatory targets of CR on potential biomarkers were obtained by combined analysis, and the relevant key targets were verified by western blotting.Results: CR improved serum and liver homogenate indexes and alleviated liver histological injury. Compared with ANIT group, the CR group had 76 differential metabolites, and 10 metabolic pathways were enriched. There were 473 DEGs significantly changed after CR treatment, most of which were enriched in the retinol metabolism, calcium signaling pathway, PPAR signaling pathway, circadian rhythm, chemokine signaling pathway, arachidonic acid metabolism, bile secretion, primary bile acid biosynthesis, and other pathways. By constructing the “compound-reaction-enzyme-gene” interaction network, three potential key-target regulation biomarkers were obtained, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), ATP-binding cassette transporter G5 (ABCG5), and sulfotransferase2A1(SULT2A1), which were further verified by western blotting. Compared with the ANIT group, the CR group significantly increased the expression of ABCG5 and SULT2A1, and the expression of HMGCR significantly decreased.Conclusion: Combined metabolomic and transcriptomic analyses show that CR has a therapeutic effect on IC through regulation of the biosynthesis of bile acids and bilirubin in the bile secretion pathway and regulation of the expression of HMGCR, ABCG5, and SULT2A1