Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological ...processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP-1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP-1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP-1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP-1 with morpholino oligomers leads to partial (PP-lα knockdown) or complete (PP-lβ or PP-lγ knockdown) death of the injected embryos. The survived embryos from PP-1α knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP-1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream targets mediating the effects of PP-1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP-1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.
Purpose
Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal ...osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US).
Methods
A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients.
Results
In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug.
Conclusion and relevance
Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.
Six isonitrogenous (390 g kg⁻¹) and isoenergetic (16.2 kJ g⁻¹) diets with varying carbohydrate : lipid (CHO : L) ratios (202.5-1.74), were fed to triplicate groups of 25 fish in indoor recirculation ...system. Over 8-week-growth trial, best weight gain (WG), specific growth rate, feed conversion ratio, protein efficiency ratio and protein production value (P < 0.05) were observed in fish-fed diets with CHO : L ratio of 7.5. Fish fed either the lowest (1.7) or highest (202.5) CHO : L ratio tended to produce lower (P < 0.05) growth and feed conversion efficiencies. The values of viscerosomatic index, hepatosomatic index and intraperitoneal fat ratio increased as dietary CHO : L ratios decreased. There were no significant differences in whole body and liver crude protein among dietary treatments. Whole body and liver lipid increased as CHO : L ratios decreased. Plasma cholesterol and triacylglyceride levels increased linearly as dietary CHO : L ratios decreased. Activities of glucokinase and pyruvate kinase were stimulated by elevated levels of dietary carbohydrate; however, activities of lipase (LPS) and alkaline phosphatase were stimulated by elevated levels of dietary lipid. Based on a second-order polynomial regression analysis of WG against dietary carbohydrate and lipid levels, 275 g kg⁻¹ of carbohydrate and 59 g kg⁻¹ of lipid, corresponding to a CHO : L ratio of 4.7, in a diet holding 390 g kg⁻¹ of crude protein and 16.3 kJ g⁻¹ of gross energy, proved to be optimal for grass carp. These results indicated that utilization of dietary lipid and carbohydrate was moderate in grass carp, but the fish were a little more capable of utilizing lipid compared with carbohydrate.
We present a measurement of the azimuthal asymmetries of two charged pions in the inclusive process e+ e- arrow right pipiX, based on a data set of 62 pb super(-1) at the center-of-mass energy of ...3.65 GeV collected with the BESIII detector. These asymmetries can be attributed to the Collins fragmentation function. We observe a nonzero asymmetry, which increases with increasing pion momentum. As our energy scale is close to that of the existing semi-inclusive deep inelastic scattering experimental data, the measured asymmetries are important inputs for the global analysis of extracting the quark transversity distribution inside the nucleon and are valuable to explore the energy evolution of the spin-dependent fragmentation function.
We study the process e+e−→π+π−ψ(3686) using 5.1 fb−1 of data collected at 16 center-of-mass energy (s) points from 4.008 to 4.600 GeV by the BESIII detector operating at the BEPCII collider. The ...measured Born cross sections for e+e−→π+π−ψ(3686) are consistent with previous results, but with much improved precision. A fit to the cross section shows contributions from two structures: the first has M=4209.5±7.4±1.4 MeV/c2 and Γ=80.1±24.6±2.9 MeV, and the second has M=4383.8±4.2±0.8 MeV/c2 and Γ=84.2±12.5±2.1 MeV, where the first errors are statistical and the second systematic. The lower-mass resonance is observed in the process e+e−→π+π−ψ(3686) for the first time with a statistical significance of 5.8σ. A charged charmoniumlike structure is observed in the π±ψ(3686) invariant mass spectrum for data at s=4.416 GeV. A fit with an S-wave Breit-Wigner function yields a mass M=4032.1±2.4 MeV/c2, where the errors are statistical only. However, there are still unresolved discrepancies between the fit model and data. The width of the intermediate state varies in a wide range for different kinematic regions within the data set. Therefore, no simple interpretation of the data has been found, and a future data sample with larger statistics and more theoretical input will be required to better understand this issue.
Using 2.93 fb −1 of e+e− collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector, we report the first measurements of the absolute branching fractions of 14 hadronic ...D0(+) decays to exclusive final states with an η , e.g., D0 → K−π+η , K0Sπ0η , K+K−η , K0SK0Sη, K−π+π0η , K0Sπ+π−η , K0Sπ0π0η , and π+π−π0η ; D+ → K0Sπ+η,K0SK+η, K−π+π+η, K0Sπ+π0η, π+π+π−η , and π+π0π0η. Among these decays, the D0 → K−π+η and D+→K0Sπ+η decays have the largest branching fractions, which are B (D0 → K−π+η) = ( 1.853 ± 0.02 5 stat ± 0.03 1 syst ) % and B ( D+ → K0Sπ+η ) = ( 1.309 ± 0.03 7 stat ± 0.03 1 syst ) % , respectively. The charge-parity asymmetries for the six decays with highest event yields are determined, and no statistically significant charge-parity violation is found.
A set of 184 recombinant inbred lines (RILs) derived from soybean vars. Kefeng No.1 x Nannong 1138-2 was used to construct a genetic linkage map. The two parents exhibit contrasting characteristics ...for most of the traits that were mapped. Using restricted fragment length polymorphisms (RFLPs), simple sequence repeats (SSRs) and expressed sequence tags (ESTs), we mapped 452 markers onto 21 linkage groups and covered 3595.9 cM of the soybean genome. All of the linkage groups except linkage group F were consistent with those of the consensus map of Cregan et al. (1999). Linkage group F was divided into two linkage groups, F1 and F2. The map consisted of 189 RFLPs, 219 SSRs, 40 ESTs, three R gene loci and one phenotype marker. Ten agronomic traits-days to flowering, days to maturity, plant height, number of nodes on main stem, lodging, number of pods per node, protein content, oil content, 100-seed weight, and plot yield-were studied. Using winqtlcart, we detected 63 quantitative trait loci (QTLs) that had LOD>3 for nine of the agronomic traits (only exception being seed oil content) and mapped these on 12 linkage groups. Most of the QTLs were clustered, especially on groups B1 and C2. Some QTLs were mapped to the same loci. This pleiotropism was common for most of the QTLs, and one QTL could influence at most five traits. Seven EST markers were found to be linked closely with or located at the same loci as the QTLs. EST marker GmKF059a, encoding a repressor protein and mapped on group C2, accounted for about 20% of the total variation of days to flowering, plant height, lodging and nodes on the main stem, respectively.
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