Deriving how far structural information is transmitted through parallel homodimeric coiled‐coils: A correlation analysis of helical staggers

How local conformation is affected by local sequence is fairly well understood for alpha‐helical coiled‐coils, but less is known about how local conformation is influenced by distant features. Here, I describe an approach to detect such an effect, based on computing correlation coefficients of local out‐of‐register alignments, or so‐called “staggers” between the helices, as a function of the axial distance between the staggers. This approach requires parallel homodimers, in which each stagger can occur with two “signs,” where either one helix or the other is shifted towards the N terminus. The signs of such staggers separated by up to 12 residues are strongly correlated, indicating that the conformations of the ends of coiled‐coils are commonly influenced by attached structures. Thus, the structures of coiled‐coil residues aberrantly attached to alternative proteins, such as those resulting from leukemogenic chromosomal rearrangements, may be distinguishable from those in normal tissues, and in turn serve as targets of selective drug design. The signs of helical staggers separated by between 13 and 30 residues are moderately yet significantly correlated, indicating that some of the coiled‐coils transmit this conformational feature axially for at least 45 Å. A positive, albeit noisy, correlation also exists among tropomyosin coiled‐coils for signed staggers separated by the 40‐residue actin repeat distance, consistent with the semi‐flexible tropomyosin filament binding F‐actin and regulating skeletal muscle contraction in a partially cooperative manner. Communication of the signs of axial staggers is explained in part by minimization of main‐chain hydrogen bond deformations. © Proteins 2013. © 2012 Wiley Periodicals, Inc.     

Effects of N6, 2′-O-dibutyryl cyclic adenosine monophosphate and the leukemia inhibitory factor on embryo development of the giant freshwater prawn,Macrobrachium rosenbergii

Summary

The effects of N⁶, 2′-O-dibutyryl cyclic adenosine monophosphate (dbcAMP) and the leukemia inhibitory factor (LIF) on embryo development of the giant freshwater prawn, Macrobrachium rosenbergii, were studied. Embryos 1.5 days old were cultured in vitro in 15% artificial seawater supplemented with 0.05 mM, 0.1 mM or 0.5 mM dbcAMP, or with 10 ng/ml, 20 ng/ml or 50 ng/ml LIF for 2 days. No differences in the morphology or growth of the embryos between the supplemented and the control groups were observed. The developmental rates as revealed by the eye formation rates were not altered with either supplement. The survival rates of the embryos declined during the course of development; and, again, the rates were not altered when supplemented with dbcAMP or LIF. Although there were no significant changes in the eye formation rate in embryos supplemented with 0.05 mM dbcAMP, an increase in the hatching rate was found. In contrast, supplementation with LIF did not improve the hatching rates. Germ cell development seemed to be most affected. The number of primordial germ cells (PGCs), the progenitors of gametes, was significantly increased with both dbcAMP and LIF supplementation. However, supplementation with 0.05 mM dbcAMP and 10 ng/ml LIF combined did not provide any additional effect on this feature.     

The Role of Platelet Serotonin and Depression in the Acute Coronary Syndrome Population

Platelet serotonin has been associated with depression and coronary artery disease. Understanding the association between platelet serotonin and depressive symptoms during acute coronary syndrome (ACS) may explain some of the ACS events seen in depressed individuals. The objectives were to evaluate whether levels of platelet serotonin during an ACS event differ between individuals who screen positive or negative for depressive symptoms and to determine if a linear relationship exists. In this cross-sectional study, data were collected on 51 patients with ACS. Multiple linear regression models were examined. Platelet serotonin levels were not significantly different between the depressed and non-depressed groups (β = -4.093 and p = .293); a linear relationship was not found (β = -.254 and p = .250). In conclusion, a relationship between platelet serotonin and depressive symptoms was not found. It remains unclear if an association exists between platelet serotonin levels and depressive symptoms during hospitalization for ACS.     

Nucleophosmin mutations in acute myeloid leukemia: A tale of protein unfolding and mislocalization

Nucleophosmin (NPM1) is an abundant, ubiquitously expressed protein mainly localized at nucleoli but continuously shuttling between nucleus and cytoplasm. NPM1 plays a role in several cellular functions, including ribosome biogenesis and export, centrosome duplication, chromatin remodeling, DNA repair, and response to stress stimuli. Much of the interest in this protein arises from its relevance in human malignancies. NPM1 is frequently overexpressed in solid tumors and is the target of several chromosomal translocations in hematologic neoplasms. Notably, NPM1 has been characterized as the most frequently mutated gene in acute myeloid leukemia (AML). Mutations alter the C‐terminal DNA‐binding domain of the protein and result in its aberrant nuclear export and stable cytosolic localization. In this review, we focus on the leukemia‐associated NPM1 C‐terminal domain and describe its structure, function, and the effect exerted by leukemic mutations. Finally, we discuss the possibility to target NPM1 for the treatment of cancer and, in particular, of AML patients with mutated NPM1 gene.     

Studies on Polyoxins,Antifungal Antibiotics

Seven additional components, polyoxins C, D, E, F, G, H and I were isolated from polyoxin complex. They have molecular formulae corresponding to C₁₁H₁₅N₃O₈, C₁₇H₂₃N₅O₁₄, C₁₇H₂₃N₅O₁₃, C₂₃H₃₀N₆O₁₅, C₁₇H₂₅N₅O₁₂, C₂₃H₃₂N₆O₁₃ and C₁₉H₂₄N₄O₁₂, respectively. These polyoxins except inactive polyoxins C and I were highly active against various kinds of phytopathogenic fungi. The close structural similarity among them including polyoxins A and B is also discussed.     

Studies on the Induced Synthesis of Maleate cis-trans Isomerase by Malonate

Maleate cis-trans isomerase in Alcaligenes faecalis IB–14 was induced by malonate and purified about 100-fold over the crude cell-free extract by treatments of ammonium sulfate fractionation, Sephadex G–100 gel filtration, DEAE-cellulose and DEAE-Sephadex A–50 column chromatography. The preparation was shown to be monodisperse on ultracentrifugal analysis and Svedberg value was found to be 3.84 S.

The enzyme was most active at pH value around 8.3 and was stable over the range of pH 5.0 to 7.0 in the presence of dithiothreitol (DTT) for a few weeks, but in the absence of it, the enzyme activity was markedly decreased, especially in the alkaline region. The enzyme activity was inhibited by various sulfhydryl reagents and oxidizing agents, whereas it was not affected by metal chelating agents. The inhibition by Hg²⁺ and PCMB was overcome by the addition of sulfhydryl compounds such as DTT, 2-mercaptoethanol, l-cysteine and glutathione. It was observed that the enzyme did not require co-factor for its function.

Kinetic studies showed that Michaelis constant for maleate was 2.8×10^?3 m and the enzyme did not catalyze the reverse reaction.     

双歧杆菌三联活菌胶囊联合营养支持治疗重症急性胰腺炎的临床研究

目的:探讨双歧杆菌三联活菌胶囊联合营养支持治疗重症急性胰腺炎的临床疗效。方法:选择2014年1月至2015年6月我院收治的90例重症急性胰腺炎患者作为研究对象,按照随机数字表法分为治疗组和对照组,每组45例患者。对照组在常规治疗基础上采用营养支持治疗,治疗组在对照组的基础上采用双歧杆菌三联活菌胶囊治疗。分别于治疗前后取患者静脉血进行C反应蛋白、白细胞介素-8、肿瘤坏死因子、白细胞计数、淀粉酶、脂肪酶、乳酸脱氢酶的检测,并对治疗效果和胃肠功能进行评分。结果:治疗组的总有效率95.56%显著高于对照组的80.00%,差异有统计学意义(P0.05)。治疗14 d后,两组患者的C反应蛋白、白细胞介素-8、肿瘤坏死因子、白细胞计数、淀粉酶、脂肪酶、乳酸脱氢酶水平均降低,且治疗组的下降幅度显著大于对照组,差异均有统计学意义(P0.05)。治疗后两组患者的胃肠功能评分均低于治疗前,且治疗组胃肠功能评分明显优于对照组,差异有统计学意义(P0.05)。结论:双歧杆菌三联活菌胶囊联合营养支持治疗重症急性胰腺炎可降低患者的血液指标,增强肠道功能,具有较好的临床疗效,临床可推广应用。     

急性非ST 段抬高性心肌梗死患者血清尿酸水平与N末端B 型钠尿肽原的相关性分析

目的:探讨急性非ST段抬高性心肌梗死(NSTEMI)患者血清尿酸水平与N末端B型钠尿肽原(NT-pro BNP)的相关性分析。方法:将143例NSTEMI患者按照入院时血清尿酸四分位数分为四组:Ⅰ组(尿酸284.18μmol/L)、Ⅱ组(284.19~336.53μmol/L),Ⅲ组(336.54~390.78μmol/L),Ⅳ(尿酸390.79μmol/L);按照血清NT-pro BNP中位数分为2组:NT-pro BNP571.56 pg/m L组和NT-pro BNP≥571.56 pg/m L组;比较各组相关指标的差异。结果:Ⅰ组、Ⅱ组、Ⅲ组及Ⅳ组四组的NT-pro BNP、GRACE危险评分、CK-MB、LEVF、c Tn I比较统计学差异(P0.05),Ⅳ组NT-pro BNP、GRACE危险评分、c Tn I、CK-MB高于Ⅰ组、Ⅱ组、Ⅲ组,Ⅲ组高于Ⅰ组、Ⅱ组(P0.05);NT-pro BNP≥571.56 pg/m L组血清尿酸、GRACE危险评分、c Tn I、CK-MB高于NT-pro BNP571.56pg/m L组(P0.05)。血清尿酸分别与NT-pro BNP、GRACE危险评分呈现正相关(P0.05)。结论:血清尿酸水平与NSTEMI患者的NT-pro BNP密切相关,临床检测血清尿酸水平对于评估NSTEMI患者NT-pro BNP水平具有重要的意义。