Predicting RNA secondary structures with pseudoknots by MCMC sampling

The most probable secondary structure of an RNA molecule, given the nucleotide sequence, can be computed efficiently if a stochastic context-free grammar (SCFG) is used as the prior distribution of the secondary structure. The structures of some RNA molecules contain so-called pseudoknots. Allowing all possible configurations of pseudoknots is not compatible with context-free grammar models and makes the search for an optimal secondary structure NP-complete. We suggest a probabilistic model for RNA secondary structures with pseudoknots and present a Markov-chain Monte-Carlo Method for sampling RNA structures according to their posterior distribution for a given sequence. We favor Bayesian sampling over optimization methods in this context, because it makes the uncertainty of RNA structure predictions assessable. We demonstrate the benefit of our method in examples with tmRNA and also with simulated data. McQFold, an implementation of our method, is freely available from http://www.cs.uni-frankfurt.de/~metzler/McQFold.     

基于"经筋理论"针刀治疗对早中期膝骨关节炎患者骨代谢指标和血清TIMP-1、MMP-3、MMP-13的影响

摘要 目的：探讨基于"经筋理论"针刀治疗对早中期膝骨关节炎（KOA）患者骨代谢指标和血清金属蛋白酶抑制物-1（TIMP-1）、基质金属蛋白酶（MMP）-3、MMP-13的影响。方法：根据随机数字表法,将2021年1月至2023年1月期间就诊于新疆医科大学附属第一医院的120例早中期KOA患者分为对照组（n=60,常规治疗）和研究组（n=60,对照组的基础上接受"经筋理论"针刀治疗）。对比两组疗效、量表评分[疼痛视觉模拟评分（VAS）、西安大略和麦克马斯特大学骨关节炎调查表（WOMAC）]、骨代谢指标[抗酒石酸盐酸性磷酸酶异构体（TRACP-5b）、骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）]和血清TIMP-1、MMP-3、MMP-13。结果：与对照组相比,研究组的临床总有效率更高（P<0.05）。与对照组相比,研究组治疗后WOMAC、VAS评分和血清MMP-3、MMP-13、TRACP-5b水平更低,TIMP-1、BALP、BGP水平更高（P<0.05）。结论：基于"经筋理论"针刀治疗早中期KOA患者,可有效减轻疼痛症状,提高临床治疗效果,可能与改善骨代谢指标和血清TIMP-1、MMP-3、MMP-13水平有关。     

血清FKN、APC与老年社区获得性肺炎患者病情和预后不良的关系

摘要 目的：探讨血清分形趋化因子（FKN）、活化蛋白C（APC）与老年社区获得性肺炎（CAP）患者病情和预后不良的关系。方法：选取2020年1月～2023年1月潍坊市人民医院收治的314例老年CAP患者为CAP组,根据病情程度分为低危组104例、中危组123例、高危组87例,根据入院30d生存状况分为死亡组65例和存活组249例,另选取同期100名体检健康老年人为对照组。采用酶联免疫吸附法检测血清FKN、APC水平。采用受试者工作特征（ROC）曲线分析血清FKN、APC水平对老年CAP患者预后不良的预测价值。通过多因素Logistic回归分析老年CAP患者预后不良的影响因素。结果：与对照组比较,CAP组血清FKN水平升高,APC水平降低（P＜0.05）。低危组、中危组、高危组老年CAP患者血清FKN水平依次升高,APC水平依次降低（P＜0.05）。多因素Logistic回归分析显示,病情高危、机械通气和C反应蛋白（CRP）、FKN升高为老年CAP患者预后不良的独立危险因素,APC升高为其独立保护因素（P＜0.05）。ROC曲线分析显示,FKN、APC水平单独和联合预测老年CAP患者预后不良的曲线下面积分别为0.783、0.789、0.870,二者联合对老年CAP患者预后不良的预测价值大于各指标单独预测。结论：血清FKN水平升高和APC水平降低参与着老年CAP患者病情进展,血清FKN联合APC能较好地预测老年CAP患者预后不良。     

The pp60c-Src inhibitor PP1 is non-competitive against ATP

The C7-cyclitol 2-epi-5-epi-valiolone is the first precursor of the cyclitol moiety of the -glucosidase inhibitor acarbose in Actinoplanes sp. SE50. The 2-epi-5-epi-valiolone becomes phosphorylated at C7 by the ATP dependent kinase AcbM prior to the next modifications. Preliminary data gave evidences that the AcbO protein could catalyse the first modification step of 2-epi-5-epi-valiolone-7-phosphate. Therefore, the AcbO protein, the encoding gene of which is also part of the acbKMLNOC operon, was overproduced and purified. Indeed the purified protein catalysed the 2-epimerisation of 2-epi-5-epi-valiolone-7-phosphate. The chemical structure of the purified reaction product was proven by nuclear magnetic resonance spectroscopy to be 5-epi-valiolone-7-phosphate.     

Amygdala protein kinase C epsilon regulates corticotropin-releasing factor and anxiety-like behavior

Corticotropin-releasing factor (CRF), its receptors, and signaling pathways that regulate CRF expression and responses are areas of intense investigation for new drugs to treat affective disorders. Here, we report that protein kinase C epsilon (PKCɛ) null mutant mice, which show reduced anxiety-like behavior, have reduced levels of CRF messenger RNA and peptide in the amygdala. In primary amygdala neurons, a selective PKCɛ activator, ψɛRACK, increased levels of pro-CRF, whereas reducing PKCɛ levels through RNA interference blocked phorbol ester-stimulated increases in CRF. Local knockdown of amygdala PKCɛ by RNA interference reduced anxiety-like behavior in wild-type mice. Furthermore, local infusion of CRF into the amygdala of PKCɛ^−/− mice increased their anxiety-like behavior. These results are consistent with a novel mechanism of PKCɛ control over anxiety-like behavior through regulation of CRF in the amygdala.     

Regulation of Na/K/Cl cotransport in vascular smooth muscle cells

The regulation of Na/K/Cl cotransport was investigated in vascular smooth muscle cells. That a Na/K/Cl cotransport system exists was established by the finding that the ouabain insensitive K influx was sensitive to the "loop" diuretic bumetanide. Furthermore, bumetanide sensitive K influx was dependent upon the presence of both Na and Cl in the extracellular milieu. Bumetanide sensitive K influx was inhibited by agents which elevate cellular cyclic AMP levels, and to a lesser extent by agents which elevate cellular cyclic GMP levels. When serum, EGF or TPA was added, bumetanide sensitive K influx was enhanced. These results suggest that vascular smooth muscle cells have a ouabain insensitive, bumetanide sensitive Na/K/Cl cotransport system which is stimulated by serum, EGF or TPA and inhibited by cAMP or cGMP.     

The formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2‐type responses

Cryptococcus neoformans is a pathogenic yeast that can form titan cells in the lungs, which are fungal cells of abnormal enlarged size. Little is known about the factors that trigger titan cells. In particular, it is not known how the host environment influences this transition. In this work, we describe the formation of titan cells in two mouse strains, CD1 and C57BL/6J. We found that the proportion of C. neoformans titan cells was significantly higher in C57BL/6J mice than in CD1. This higher proportion of titan cells was associated with a higher dissemination of the yeasts to the brain. Histology sections demonstrated eosinophilia in infected animals, although it was significantly lower in the CD1 mice which presented infiltration of lymphocytes. Both mouse strains presented infiltration of granulocytes, but the amount of eosinophils was higher in C57BL/6J. CD1 mice showed a significant accumulation of IFN‐γ, TNF‐α and IL17, while C57BL/BL mice had an increase in the anti‐inflammatory cytokine IL‐4. IgM antibodies to the polysaccharide capsule and total IgE were more abundant in the sera from C57BL/6J, confirming that these animals present a Th2‐type response. We conclude that titan cell formation in C. neoformans depends, not only on microbe factors, but also on the host environment.     

Zinc finger structure-function in Ikaros

The zinc finger motif was used as a vehicle for the initial discovery of Ikaros in the context of T-cell differentiation and has been central to all subsequent analyses of Ikaros function. The Ikaros gene is alternately spliced to produce several isoforms that confer diversity of function and consequently have complicated analysis of the function of Ikaros in vivo. Key features of Ikaros in vivo function are associated with six C2H2 zinc fingers; four of which are alternately incorporated in the production of the various Ikaros isoforms. Although no complete structures are available for the Ikaros protein or any of its family members, considerable evidence has accumulated about the structure of zinc fingers and the role that this structure plays in the functions of the Ikaros family of proteins. This review summarizes the structural aspects of Ikaros zinc fingers, individually, and in tandem to provide a structural context for Ikaros function and to provide a structural basis to inform the design of future experiments with Ikaros and its family members.     

Properties of the reaction center of the thermophilic purple photosynthetic bacterium Chromatium tepidum

Reaction centers were purified from the thermophilic purple sulfur photosynthetic bacterium Chromatium tepidum. The reaction center consists of four polypeptides L, M, H and C, whose apparent molecular masses were determined to be 25, 30, 34 and 44 kDa, respectively, by polyacrylamide gel electrophoresis. The heaviest peptide corresponds to tightly bound cytochrome. The tightly bound cytochrome c contains two types of heme, high-potential c-556 and low-potential c-553. The low-potential heme is able to be photooxidized at 77 K. The reaction center exhibits laser-flash-induced absorption changes and circular dichroism spectra similar to those observed in other purple photosynthetic bacteria. Whole cells contain both ubiquinone and menaquinone. Reaction centers contain only a single active quinone; chemical analysis showed this to be menaquinone. Reaction center complexes without the tightly bound cytochrome were also prepared. The near-infrared pigment absorption bands are red-shifted in reaction centers with cytochrome compared to those without cytochrome.