Inference of patient‐specific subpathway activities reveals a functional signature associated with the prognosis of patients with breast cancer

Breast cancer is one of the most deadly forms of cancer in women worldwide. Better prediction of breast cancer prognosis is essential for more personalized treatment. In this study, we aimed to infer patient‐specific subpathway activities to reveal a functional signature associated with the prognosis of patients with breast cancer. We integrated pathway structure with gene expression data to construct patient‐specific subpathway activity profiles using a greedy search algorithm. A four‐subpathway prognostic signature was developed in the training set using a random forest supervised classification algorithm and a prognostic score model with the activity profiles. According to the signature, patients were classified into high‐risk and low‐risk groups with significantly different overall survival in the training set (median survival of 65 vs 106 months, P = 1.82e‐13) and test set (median survival of 75 vs 101 months, P = 4.17e‐5). Our signature was then applied to five independent breast cancer data sets and showed similar prognostic values, confirming the accuracy and robustness of the subpathway signature. Stratified analysis suggested that the four‐subpathway signature had prognostic value within subtypes of breast cancer. Our results suggest that the four‐subpathway signature may be a useful biomarker for breast cancer prognosis.     

Molecular phylogeny of labyrinthulids and thraustochytrids based on the sequencing of 18S ribosomal RNA gene

Labyrinthulids and thraustochytrids are unicellular heterotrophs, formerly considered as fungi, but presently are recognized as members in the stramenopiles of the kingdom Protista sensu lato. We determined the 18S ribosomal RNA gene sequences of 14 strains from different species of the six genera and analyzed the molecular phylogenetic relationships. The results conflict with the current classification based on morphology, at the genus and species levels. These organisms are separated, based on signature sequences and unique inserted sequences, into two major groups, which were named the labyrinthulid phylogenetic group and the thraustochytrid phylogenetic group. Although these groupings are in disagreement with many conventional taxonomic characters, they correlated better with the sugar composition of the cell wall. Thus, the currently used taxonomic criteria need serious reconsideration.     

代表活性污泥中苯酚降解菌群的ERIC-PCR产物片段的多态性

对可能代表活性污泥中两个时期的主要苯酚降解菌群的：ERIC-PCR指纹图谱中的两条2．1kb的条带(P1和P8)中的DNA片段进行克隆、转化,得到193个转化子。．HinfⅠ物理图谱分析得到35种酶切类型,将两端各进行1次测序后,同源性大于90％的克隆归为一类,共得到10种序列类型。对各类型的代表克隆进行了全长测序,5种类型为P1条带所有,3种类型为P8所有,二者共享的类型为2种,丰度最高的片段为S3,P1条带中76．3％的转化子和P8条带中66．7％转化子属该类型。对所得序列进行检索分析,它们与GenBank中已知基因序列均无显著同源性。用S3特异性引物对活性污泥样品及其它在LB、dCGY、MP和FWM培养基上的回收菌进：行扩增,除LB上的回收菌没有显示目的条带外,活性污泥和其回收菌中均检测到带有该基因组片段的菌种的存在。研究为专一性分离降酚活性污泥中的优势菌提供了分子探针。     

弯曲菌染色体DNA限制性内切酶带型研究

从鸡、羊、鹅、鸭粪便中分离出的空肠弯曲菌,提取染色体DNA做酶切分析,得到几乎相同的带型;与从比利时引进的结肠弯曲菌及海鸥弯曲菌比较,带型完全不同;同时,从人胃粘膜中分离出的幽门螺旋菌,做染色体DNA酶切分析,得到与前者完全不同的带型。     

利用蛋白质序列模式识别改善谷氨酸棒杆菌基因组注释

即使细菌基因组的基因结构较为简单,但在注释过程中也可能出现基因遗漏的现象。当潜在基因在高质量数据库中没有显著同源序列时,基于知识库的基因预测方法就会遇到困难。本文希望通过系统扫描基因组所有可能ORF的蛋白质序列模式来搜索遗漏基因。为验证该方法的可行性,作者系统分析了重要的工业发酵微生物谷氨酸棒杆菌的基因组,发现了25个候选疑似基因。它们具有显著的蛋白质序列模式,但在Swiss-Prot中元显著同源序列,并且在GenBank中仍未注释。深入分析发现,25个候选疑似基因中19个为可能基因,3个为可能假基因,3个为疑似基因序列。这些结果说明本文的分析方法可以有效地用于无显著同源序列基因的搜索。     

普米克令舒雾化吸入对早期声带癌CO2激光术后影响

目的：观察早期声带癌患者CO2激光手术后应用普米克令舒雾化吸入治疗的临床效果。方法：将CO2激光喉早期声带癌显微手术后患者120例随机分成2组,其中实验组60例应用普米克令舒雾化吸入,每日2次,每次1 mg;对照组60例采用地塞米松5 mg,庆大霉素8万u,糜蛋白酶4000u日2次混合雾化吸入,同时使用7天,对比2组术后呼吸困难、粘膜水肿、发热、声嘶、疼痛等发生情况效果。结果：实验组的患者,术后愈复天数、呼吸困难及咳嗽发生率明显低于对照组,差异有显著性意义（P〈0.05）,而术后发热情况及声音嘶哑情况二者无明显差异（P〉0.05）。结论：普米克令舒雾化吸入能有效缩短喉CO2激光显微外科手术患者的痊愈时间。     

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design

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Lipoprotein size is a main determinant for the rate of hydrolysis by exogenous LPL in human plasma

LPL is a key player in plasma triglyceride metabolism. Consequently, LPL is regulated by several proteins during synthesis, folding, secretion, and transport to its site of action at the luminal side of capillaries, as well as during the catalytic reaction. Some proteins are well known, whereas others have been identified but are still not fully understood. We set out to study the effects of the natural variations in the plasma levels of all known LPL regulators on the activity of purified LPL added to samples of fasted plasma taken from 117 individuals. The enzymatic activity was measured at 25°C using isothermal titration calorimetry. This method allows quantification of the ability of an added fixed amount of exogenous LPL to hydrolyze triglyceride-rich lipoproteins in plasma samples by measuring the heat produced. Our results indicate that, under the conditions used, the normal variation in the endogenous levels of apolipoprotein C1, C2, and C3 or the levels of angiopoietin-like proteins 3, 4, and 8 in the fasted plasma samples had no significant effect on the recorded activity of the added LPL. Instead, the key determinant for the LPL activity was a lipid signature strongly correlated to the average size of the VLDL particles. The signature involved not only several lipoprotein and plasma lipid parameters but also apolipoprotein A5 levels. While the measurements cannot fully represent the action of LPL when attached to the capillary wall, our study provides knowledge on the interindividual variation of LPL lipolysis rates in human plasma.     

An integrated mRNA-lncRNA signature for relapse prediction in laryngeal cancer

Patients with laryngeal cancer with early relapse usually have a poor prognosis. In this study, we aimed to identify a multi-gene signature to improve the relapse prediction in laryngeal cancer. One microarray data set GSE27020 (training set, N = 109) and one RNA-sequencing data set (validation set, N = 85) were included into the analysis. In the training set, the microarray expression profile was re-annotated into an mRNA-long noncoding RNA (lncRNA) biphasic profile. Then, LASSO Cox regression model identified nine relapse-related RNA (eight mRNA and one lncRNA), and a risk score was calculated for each sample according to the model coefficients. Patients with high-risk showed poorer relapse-free survival than patients with low risk (hazard ratios (HR): 6.189, 95% confidence interval (CI): 3.075-12.460, P < 0.0001). The risk score demonstrated good accuracy in predicting the relapse (area under time-dependent receiver-operating characteristic (AUC): 0.859 at 1 year, 0.822 at 3 years, and 0.815 at 5 years). The results were validated in the validation set (HR: 3.762, 95% CI: 1.594-8.877, P = 0.011; AUC: 0.770 at 1 year, 0.769 at 3 years, and 0.728 at 5 years). The multivariate analysis reached consistent results after adjustment by multiple confounders. When compared with a 27-gene signature, a 2-lncRNA signature, and Tumor-Node-Metastasis stage, the risk score also showed better performance (P < 0.05). In conclusion, we successfully developed a robust mRNA-lncRNA signature that can accurately predict the relapse in laryngeal cancer.