Properties of Markov Chain Monte Carlo Performance across Many Empirical Alignments

Nearly all current Bayesian phylogenetic applications rely on Markov chain Monte Carlo (MCMC) methods to approximate the posterior distribution for trees and other parameters of the model. These approximations are only reliable if Markov chains adequately converge and sample from the joint posterior distribution. Although several studies of phylogenetic MCMC convergence exist, these have focused on simulated data sets or select empirical examples. Therefore, much that is considered common knowledge about MCMC in empirical systems derives from a relatively small family of analyses under ideal conditions. To address this, we present an overview of commonly applied phylogenetic MCMC diagnostics and an assessment of patterns of these diagnostics across more than 18,000 empirical analyses. Many analyses appeared to perform well and failures in convergence were most likely to be detected using the average standard deviation of split frequencies, a diagnostic that compares topologies among independent chains. Different diagnostics yielded different information about failed convergence, demonstrating that multiple diagnostics must be employed to reliably detect problems. The number of taxa and average branch lengths in analyses have clear impacts on MCMC performance, with more taxa and shorter branches leading to more difficult convergence. We show that the usage of models that include both Γ-distributed among-site rate variation and a proportion of invariable sites is not broadly problematic for MCMC convergence but is also unnecessary. Changes to heating and the usage of model-averaged substitution models can both offer improved convergence in some cases, but neither are a panacea.     

MicroRNA-411a-3p过表达抑制Ca2+信号转导与羊驼黑色素细胞的增殖和迁移

黑色素细胞中产生的黑色素转移及黑色素细胞的增殖和迁移均与色素沉积有关。黑色素细胞的增殖需要有丝分裂原协同进行。黑色素细胞的增殖和分化受组织环境以及多种毛色基因的调控。miRNA-411a-3p在不同毛色羊驼皮肤中呈差异表达,且通过靶向IGF1R调控黑色素生成。但miRNA-411a-3p是否与黑色素颗粒迁移、黑色素细胞的增殖和迁移相关未见报道。本研究通过miRNA-411a-3p转染羊驼黑色素细胞后发现,与对照组相比,钙离子信号转导水平下降了（91.73±1.53）% (P<0.01),与黑色素转移有关的Rab27a和肌球蛋白Va在蛋白质水平的表达均被下调,同时与细胞增殖有关的整联蛋白β1和β5相关基因在转录水平分别下降了（44.67 ± 13.67）%（P<0.01）和（30.72 ± 6.23）% (P<0.01),在蛋白质水平表达下降了（45.18 ± 1.96）% (P<0.001)和（11.52 ± 1.09）% (P<0.001)。综上所述,miRNA-411a-3p过表达后会抑制钙离子信号转导,以及羊驼黑色素细胞的增殖和迁移。     

MicroRNA-411a-3p过表达抑制Ca2+信号转导与羊驼黑色素细胞的增殖和迁移

黑色素细胞中产生的黑色素转移及黑色素细胞的增殖和迁移均与色素沉积有关。黑色素细胞的增殖需要有丝分裂原协同进行。黑色素细胞的增殖和分化受组织环境以及多种毛色基因的调控。miRNA-411a-3p在不同毛色羊驼皮肤中呈差异表达,且通过靶向IGF1R调控黑色素生成。但miRNA-411a-3p是否与黑色素颗粒迁移、黑色素细胞的增殖和迁移相关未见报道。本研究通过miRNA-411a-3p转染羊驼黑色素细胞后发现,与对照组相比,钙离子信号转导水平下降了（91.73±1.53）% (P<0.01),与黑色素转移有关的Rab27a和肌球蛋白Va在蛋白质水平的表达均被下调,同时与细胞增殖有关的整联蛋白β1和β5相关基因在转录水平分别下降了（44.67 ± 13.67）%（P<0.01）和（30.72 ± 6.23）% (P<0.01),在蛋白质水平表达下降了（45.18 ± 1.96）% (P<0.001)和（11.52 ± 1.09）% (P<0.001)。综上所述,miRNA-411a-3p过表达后会抑制钙离子信号转导,以及羊驼黑色素细胞的增殖和迁移。     

外源抗坏血酸缓解水稻幼苗的铝胁迫效应

为探讨外源抗坏血酸对铝胁迫下水稻氧化损伤的影响,该文以峰1A(不育系,籼稻)和滇优35号(杂交,粳稻)两个水稻品种为材料,采用溶液培养法研究外源抗坏血酸(AsA)对50μmol·L^-1Al³⁺胁迫下水稻根尖H₂O₂和内源AsA含量以及抗氧化酶活性的影响。结果表明:铝胁迫24 h时,水稻根尖内源AsA含量为对照的0.90倍,与对照相比,根尖H₂O₂增加了0.55倍至1.3倍,SOD、POD、CAT及APX活性分别增加了0.83倍至1.6倍、1.0倍至1.3倍、0.85倍至1.2倍、1.0倍至1.8倍;外源AsA处理铝胁迫水稻24 h,水稻根尖内源AsA含量为对照的1.2倍,SOD、POD、CAT及APX活性分别增加了1.2倍至2.2倍、1.5倍至1.6倍、1.3倍至1.7倍、1.2倍至2.6倍,根尖H₂O₂含量增加了0.1倍至0.6倍。这些研究结果说明铝胁迫加剧了细胞膜的过氧化程度,并诱导抗氧化酶活性以清除活性氧,...     

CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins

The calcium-calmodulin–dependent protein kinase kinase-2 (CaMKK2) is a key regulator of cellular and whole-body energy metabolism. It is known to be activated by increases in intracellular Ca²⁺, but the mechanisms by which it is inactivated are less clear. CaMKK2 inhibition protects against prostate cancer, hepatocellular carcinoma, and metabolic derangements induced by a high-fat diet; therefore, elucidating the intracellular mechanisms that inactivate CaMKK2 has important therapeutic implications. Here we show that stimulation of cAMP-dependent protein kinase A (PKA) signaling in cells inactivates CaMKK2 by phosphorylation of three conserved serine residues. PKA-dependent phosphorylation of Ser⁴⁹⁵ directly impairs calcium-calmodulin activation, whereas phosphorylation of Ser¹⁰⁰ and Ser⁵¹¹ mediate recruitment of 14-3-3 adaptor proteins that hold CaMKK2 in the inactivated state by preventing dephosphorylation of phospho-Ser⁴⁹⁵. We also report the crystal structure of 14-3-3ζ bound to a synthetic diphosphorylated peptide that reveals how the canonical (Ser⁵¹¹) and noncanonical (Ser¹⁰⁰) 14-3-3 consensus sites on CaMKK2 cooperate to bind 14-3-3 proteins. Our findings provide detailed molecular insights into how cAMP-PKA signaling inactivates CaMKK2 and reveals a pathway to inhibit CaMKK2 with potential for treating human diseases.     

Effect of Ga3+ and Gd3+ ions substitution on the structural and optical properties of Ce3+‐doped yttrium aluminium garnet phosphor nanopowders

The structural and optical properties of commercially obtained Y₃Al₅O₁₂:Ce³⁺ phosphor were investigated by replacing Al³⁺ with Ga³⁺ and Y³⁺ with Gd³⁺ in the Y₃Al₅O₁₂:Ce³⁺ structure to form Y₃(Al,Ga)₅O₁₂:Ce³⁺ and (Y,Gd)₃Al₅O₁₂:Ce³⁺. X‐Ray diffraction (XRD) results showed slight 2‐theta peak shifts to lower angles when Ga³⁺ was used and to higher angles when Gd³⁺ was used, with respect to peaks from Y₃Al₅O₁₂:Ce³⁺ and JCPDS card no. 73–1370. This could be attributed to induced crystal‐field effects due to the different ionic sizes of Ga³⁺ and Gd³⁺ compared with Al³⁺ and Y³⁺. The photoluminescence (PL) spectra showed broad excitation from 350 to 550 nm with a maximum at 472 nm, and broad emission bands from 500 to 650 nm, centred at 578 nm for Y₃Al₅O₁₂:Ce³⁺ arising from the 5d → 4f transition of Ce³⁺. PL revealed a blue shift for Ga³⁺ substitution and a red shift for Gd³⁺ substitution. UV–Vis showed two absorption peaks at 357 and 457 nm for Y₃Al₅O₁₂:Ce³⁺, with peaks shifting to 432 nm for Ga³⁺ and 460 nm for Gd³⁺ substitutions. Changes in the trap levels or in the depth and number of traps due to Ce³⁺ were analysed using thermoluminescence (TL) spectroscopy. This revealed the existence of shallow and deep traps. It was observed that Ga³⁺ substitution contributes to the shallowest traps at 74 °C and fewer deep traps at 163 °C, followed by Gd³⁺ with shallow traps at 87 °C and deep traps at 146 °C. Copyright © 2016 John Wiley & Sons, Ltd.     

A non-chromatographic radioimmunoassay of estrone and estradiol-17beta serum

A sensitive and efficient non-chromatographic procedure employing the Girard reagent and solvent-partitioning has been developed for the accurate radioimmunoassay (RIA) of estrone (E1) and estradiol-17β(E2) in a single 1.0 ml specimen of male or female serum. Using standard curves which permitted the discrimination of zero from 0.75–1.5 pg (p=0.05), the following mean procedural blanks (pg ± S.D.) were determined (1.0 ml water, n= 24): estrone, 2. 1 ± 1.1 (range 0–4.1); estradiol 1.0± 1.1 (range 0–3.6).A comparison of RIA of estrogens (1) in serum after separation by the Girard procedure and by TLC yielded correlation coefficients of 0.99 and 0.98 for E1 and E2 respectively. The following results (pg/ml ± S.D.) were obtained on RIA of E1 and E2 in 12 different 1.0 ml specimens of male and female serum using the Girard procedure: male. E1 (32.0 ± 9.2), E2 (24.1 ± 10.9); female, E1 (108.5 ± 60.8), E2 (126.4 ± 63.2).The intra-assay variability (c.v.) was found to be 12.6% for E1 and 9.4% for E2. The interassay variability was 14.2% for both estrogens.Twenty-four assays of E1 and E2 can be completed by one person in 2 working days.     

黄芪对BALB/C小鼠感染Coxsackie B_3病毒后T细胞免疫的影响

本文用抗原特异性细胞毒技术检测小鼠感染coxsackie B_3病毒后并腹腔注射黄芪一周在5—28天脾脏、外周血及心肌中T淋巴细胞亚群分布的变化情况。结果显示:黄芪治疗组小鼠外周血、脾脏中Thy1+细胞百分率在感染后第7—14天明显增高(P<0.05),在心肌中则低于同期生理盐水组。L3T4+淋巴细胞百分率黄芪治疗组在病毒感染后5—14天的脾脏,第9天的外周血和第7、14天的心肌中显著低于生理盐水组,而Lyt2+淋巴细胞百分率两实验组间均无统计学差异,提示中药黄芪对急性病毒性心肌炎小鼠T细胞免疫具有明显的调节作用,且主要是通过调节Thy1+和L3T4+淋巴细胞亚群而起到治疗目的的。     

Identification of some plasma metabolites of 6, 7-3-H-estrone glucosiduronate in male dogs.

Following the constant infusion of 6, 7-3-H-estrone glucosiduronate in male dogs for a period of 120 minutes, the radioactive metabolites present in the plasma were separated by solvent partition, DEAE-Sephapadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and steroids and their derivatives. Most of the radioactivity in the plasma was identified as estrone glucosiduronate. The major metabolite present was estradiol-17-beta-3-glucosiduronate. Small amounts of estradiol-17-alpha-3-glucosiduronate and free estrone were also identified. Three other minor conjugates were separated, but positive identification could not be made.     

稀土离子(La~(3+)、Nd~(3+)、Ho~(3+)、Yb~(3+))对人红细胞膜Na~+/K~+ ATPase作用的初步研究

本文以低渗法从新鲜健康人红细胞中制得膜Na~+/K~+ ATPase,用于研究四种鑭系稀土离子(La~(3+)、Nd~(3+)、Ho~(3+)、Yb~(3+))对该酶的影响。结果表明,四种鑭系离子都对红细胞膜Na~+/K~+ ATPase的活性有抑制作用。当反应体系中的稀土离子浓度达50μmol/L时,Na~+/K~+ ATPase的活性所剩不多;低于50μmol/L鑭系离子时,以Nd~(3+)的抑制作用最强;金属离子螯合剂能阻止稀土离子对Na~+/K~+ ATPase的抑制作用。此项研究为稀土的生物效应的理论提供了一些新的证据。     

Yb3+-儿茶素配合物的抑菌活性及其机理探究

本文对Yb~(3+)-儿茶素配合物(Yb~(3+)-C)的合成、抑菌活性及抑菌机理展开了系统研究.结果表明,合成配合物Yb~(3+)-C的最适摩尔比为1∶4.Yb~(3+)-C的最小抑菌浓度(MIC)均显著低于Yb~(3+)和C,对大肠杆菌(Escherichia coli)、金黄色葡萄球菌(Staphylococcus aureus)、绿脓杆菌(Pseudomonas aeruginosa)及沙门氏菌(Salmonella)均有较强的抑菌作用,而对金黄色葡萄球菌抑制作用更强,其MIC值低至0.0963 mmol/L.进一步研究表明,Yb~(3+)-C仅需要2 h就能杀灭细菌,可有效缩短杀菌时间.此外,扫描电镜(SEM)、透射电镜(TEM)观察结果以及Yb~(3+)在细胞膜和细胞内的吸收和分布表明,Yb~(3+)-C对细胞具有更强的亲和力与穿透力,使Yb~(3+)更容易在细胞质中累积至有效浓度,从而造成细胞结构的破坏,并引起细胞凋亡.     

GM3与Ca2+-ATP酶的重建及其冷冻断裂电镜观察

应用生物膜的分离与重建技术, 将GM3、大豆磷脂与肌质网Ca²⁺-ATP酶共同重建在脂质体上, 酶活力明显增加. 经负染、冷冻断裂复型后电镜等形态学方法证实形成的脂酶体囊泡封闭性好,脂酶体上Ca²⁺-ATP酶蛋白颗粒均匀、直径增大.     

Association of 14-3-3 proteins with the C-terminal autoinhibitory domain of the plant plasma-membrane H+-ATPase generates a fusicoccin-binding complex

The plant plasma-membrane H⁺-ATPase (EC 3.6.1.35) contains a C-terminal autoinhibitory domain whose displacement from the catalytic site is caused by treatment of intact plant tissue with the phytotoxin fusicoccin (FC). The FC-induced activation of the H⁺-ATPase was proposed to involve a direct interaction of 14-3-3 proteins with the H⁺-ATPase. By analysing plasma membranes derived from leaves of Commelina communis L., direct biochemical evidence has now been obtained for a complex between the C-terminus of the H⁺-ATPase and a 14-3-3 dimer. Stabilization of this complex was achieved by FC treatment in vivo or in vitro. Furthermore, the C-terminal domain of the H⁺-ATPase in association with a 14-3-3 dimer is essential for the creation of a functional FC-binding complex. Received: 1 August 1998 / Accepted: 15 September 1998     

Gas chromatography profile of estrogens: Application to pregnancy urine

A method for the simultaneous quantitation of 7 estrogens in pregnancy urine is described. It involves enzymatic hydrolysis, extraction of free steroids, ion-exchange column chromatography and quantitation of the trimethylsilyl derivatives by gas chromatography on OV 1. Data obtained from normal and twin pregnancies and from women with anencephalic fetus or intra uterine fetal death are analysed. The sensibility of the method is about 40 μg of each estrogen by liter of urine.     

Thermoluminescence dosimetric attributes of Yb3+-doped BaO–ZnO–LiF–B2O3 glass material after Er3+ co-doping

Motivated by our previous study on Sm³⁺ ions as thermoluminescence (TL) sensitizers to the BaO–ZnO–LiF–B₂O₃–Yb₂O₃ glass system, in the current study we examined the effect of Er³⁺ ion co-doping on the TL characteristics of this glass system. The 4f–4f electronic transitions of the Er³⁺ and Yb³⁺ ions were confirmed via the optical absorption spectrum. Notably, the use of Yb³⁺–Er³⁺ ions failed to improve the TL intensity, sensitivity, and trap density. However, they enabled the glass system to function as an activator–quencher system. The linearity range and effective atomic number remained unaffected after co-doping. In addition, the problem of anomalous fading caused a remnant signal of just 58% after a week of storage of the Yb³⁺ monodoped glass. This was resolved by the optimum co-doping of Er³⁺ ions to achieve an 89% signal. The co-doping of Er³⁺ ions to the BaO–ZnO–LiF–B₂O₃–Yb₂O₃ glass system regulated its thermal stability and therefore supplemented its potential for radiation monitoring in food processing and retrospective dosimetry.     

Altered SK3/KCa2.3-mediated migration in adenomatous polyposis coli (Apc) mutated mouse colon epithelial cells

Lost of adenomatous polyposis coli gene (Apc) disturbs the migration of intestinal epithelial cells but the mechanisms have not been fully characterized. Since we have demonstrated that SK3/KCa2.3 channel promotes cancer cell migration, we hypothesized that Apc mutation may affect SK3/KCa2.3 channel-mediated colon epithelial cell motility. We report evidence that SK3/KCa2.3 channel promotes colon epithelial cells motility. Following Apc mutation SK3/KCa2.3 expression is largely reduced leading to a suppression of the SK3/KCa2.3 channel mediated-cell migration. Our findings reveal a previously unknown function of the SK3/KCa2.3 channel in epithelial colonic cells, and suggest that Apc is a powerful regulator SK3/KCa2.3 channel.     

Assay for erythrocyte superoxide dismutase activity in patients with lung cancer and effects on pollution and smoke trace elements

The antioxidative effect of CuZnSOD, which catalyzes the dismutation of Superoxide anion (O₂-), provides a defense against the oxygen toxicity. The object of the study is to evaluate the erythrocytes Superoxide dismutase (SOD) activity in two groups of persons (Group I, healthy blood donors; Group II, lung cancer patients), using the spectrophotometric assay of NADH oxidation and the indirect method (2–27). The effect of trace elements, such as A1^3-, Cr³⁺, Fe³⁺, Hg²⁺, NI²⁺, and Pb²⁺ (producing free radicals oxygen and present in pollution and smoke) is also evaluated. The results show the decrease of SOD activity in lung cancer patients with respect to healthy individuals. Likewise, in those patients the enzymatic activity is bigger in early stage (I,II) with respect to advanced one (III) (p < 0.05). The lesser activity when the samples are incubated with Ni or Pb point out that these metals play a role in neoplasm development. In short, the oxidant-antioxidant balance is altered in lung cancer patients.     

Differentiative pathway activated by 3-aminobenzamide, an inhibitor of PARP, in human osteosarcoma MG-63 cells

This study describes the molecular mechanism by which treatment with 3-AB, a potent inhibitor of PARP, allows human osteosarcoma MG-63 cells to restrict growth and enter differentiation. Our findings show that in MG-63 cells, aberrant gene expression keeps Rb protein constitutively inactivated through hyperphosphorylation and this promotes uncontrolled proliferation of the cells. After 3-AB-treatment, the poly(ADP-ribosyl)ation of nuclear proteins markedly decreases and this results in an increase in both the hypophosphorylated active form of Rb and pRb/E2F complexes. These effects are accompanied by G1 arrest, downregulation of gene products required for proliferation (cyclin D1, beta-catenin, c-Jun, c-Myc and Id2) and upregulation of those implicated in the osteoblastic differentiation (p21/Waf1, osteopontin, osteocalcin, type I collagen, N-cadherins and alkaline phosphatase). Our study suggests that use of PARP inhibitors may induce a remodeling of chromatin with the reprogramming of gene expression and the activation of differentiation.     

Metal Ion Dependence of Cooperative Collapse Transitions in RNA

Positively charged counterions drive RNA molecules into compact configurations that lead to their biologically active structures. To understand how the valence and size of the cations influences the collapse transition in RNA, small-angle X-ray scattering was used to follow the decrease in the radius of gyration (R_g) of the Azoarcus and Tetrahymena ribozymes in different cations. Small, multivalent cations induced the collapse of both ribozymes more efficiently than did monovalent ions. Thus, the cooperativity of the collapse transition depends on the counterion charge density. Singular value decomposition of the scattering curves showed that folding of the smaller and more thermostable Azoarcus ribozyme is well described by two components, whereas collapse of the larger Tetrahymena ribozyme involves at least one intermediate. The ion-dependent persistence length, extracted from the distance distribution of the scattering vectors, shows that the Azoarcus ribozyme is less flexible at the midpoint of transition in low-charge-density ions than in high-charge-density ions. We conclude that the formation of sequence-specific tertiary interactions in the Azoarcus ribozyme overlaps with neutralization of the phosphate charge, while tertiary folding of the Tetrahymena ribozyme requires additional counterions. Thus, the stability of the RNA structure determines its sensitivity to the valence and size of the counterions.