Apolipoproteins and amyloid fibril formation in atherosclerosis

Amyloid fibrils arise from the aggregation of misfolded proteins into highly-ordered structures. The accumulation of these fibrils along with some non-fibrillar constituents within amyloid plaques is associated with the pathogenesis of several human degenerative diseases. A number of plasma apolipoproteins, including apolipoprotein (apo) A-I, apoA-II, apoC-II and apoE are implicated in amyloid formation or influence amyloid formation by other proteins. We review present knowledge of amyloid formation by apolipoproteins in disease, with particular focus on atherosclerosis. Further insights into the molecular mechanisms underlying their amyloidogenic propensity are obtained from in vitro studies which describe factors affecting apolipoprotein amyloid fibril formation and interactions. Additionally, we outline the evidence that amyloid fibril formation by apolipoproteins might play a role in the development and progression of atherosclerosis, and highlight possible molecular mechanisms that could contribute to the pathogenesis of this disease.     

LINC01579 promotes cell proliferation by acting as a ceRNA of miR-139-5p to upregulate EIF4G2 expression in glioblastoma

Glioblastoma (GBM), a malignant and lethal tumor, remains a big threat to human health and life. Increasing explorations have confirmed that long noncoding RNAs are involved in the tumorigenesis and development of multiple cancers. Nevertheless, the regulatory mechanism of (long intergenic nonprotein coding RNA 1579 LINC01579) in GBM remains to be investigated. In this study, the expression of LINC01579 was upregulated in GBM cells and LINC01579 knockdown inhibited cell proliferation as well as promoted cell apoptosis. Additionally, LINC01579 acted as a sponge for miR-139-5p in GBM and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) was found to be a downstream target of miR-139-5p. Furthermore, the positive correlation of LINC01579 and EIF4G2 as well as the converse correlation between miR-139-5p and LINC01579 (or EIF4G2) were revealed by the experiments. Based on rescue assays, EIF4G2 overexpression or miR-139-5p inhibitor partially recovered the function of LINC01579 knockdown on cell proliferation and apoptosis. In summary, the results of this study verified that LINC01579 modulated cell proliferation and cell apoptosis in GBM by competitively binding with miR-139-5p to regulate EIF4G2, which provided a new clue to figure out potential therapy for patients suffered from GBM.     

A Modified Valley Restrained Monte Carlo Method to Efficiently Search the Low Energy Structures of Peptides

Abstract

A new Monte Carlo sampling scheme, namely the Modified Valley Restrained Monte Carlo procedure, is used to obtain the global energy minimum conformations for polypeptides, such as Met-enkephalin and Melittin. For each peptide, we found close agreement with previous results from both theoretical and experimental studies. The simple idea for controlling the step size according to the Valley Function, provides useful suggestions in searching the global energy minimum structures, and furthermore helps solve the multiple minima problem.     

促葡萄糖转运蛋白基因家族的分子进化研究

葡萄糖转运蛋白是一个在结构上相似功能上不同的多基因家族（ＧＬＵＴ１－ＧＬＵＴ５）。由于这一组蛋白和体内的葡萄糖利用有关,因此被认为是糖尿病胰岛素抵抗（抗性）的一个候选基因。本文比较了不同种生物这一基因家族的氨基酸和核苷酸顺序;推测了亲水性和疏水性分布;计算了蛋白质和核苷酸的进化距离,并在此基础上构建了分子进化树。研究表明：这一基因家族具有高度的同源性、极为相似的亲水性和疏水性分布以及结构的对称性。提示这一基因家族起源于一个共同的祖先并可能通过基因的重复而形成。这一进化机制可能有利于氨基酸结构的稳定及抵抗突变的作用。由于邻元法构建的进化树其分支长度存在差异,提示在这一基因家族的进化过程中,各分支上的进化速率并不相同。蛋白质进化距离和核苷酸进化距离所构建进化树的差异提示了在基因组中可能存在隐匿替换。两种方法构建的进化树都提示了ＧＬＵＴ１、３、４在结构和功能上要更为保守。     

Maternal serum-derived exosomal lactoferrin as a marker in detecting and predicting ventricular septal defect in fetuses

Among different types of congenital heart diseases, ventricular septal defect is the most frequently diagnosed type and is frequently missed in early prenatal screening programs. Herein, we explored the role of maternal serum-derived exosomes in detecting and predicting ventricular septal defect in fetuses in the early stage of pregnancy. A total of 104 pregnant women consisting of 52 ventricular septal defect cases and 52 healthy controls were recruited. TMT/iTRAQ proteomic analysis uncovered 15 maternal serum exosomal proteins, which showed differential expression between ventricular septal defect and control groups. Among these, four down-regulated proteins, lactoferrin, SBSN, DCD, and MBD3, were validated by Western blot. The protein lactoferrin was additionally verified by ELISA which was able to distinguish ventricular septal defects from controls with area under the ROC curve (AUC) 0.804 (p < 0.001). Our findings reveal that lactoferrin in maternal serum-derived exosomes may be a potential biomarker for non-invasive prenatal diagnosis of fetal ventricular septal defects.     

Phenology of the rhodomelarian algae Neorhodomela aculeata and Ceramium kondoi and their survival strategies against herbivorous snails

The seasonal growth and reproductive phenology of Neorhodomela aculeata (Perestenko) Masuda and Ceramium kondoi Yendo, and the food preferences of herbivorous snails were examined to elucidate (i) why snails select the fronds of N. aculeata for their habitat; and (ii) the survival strategies of the two red algae under grazing pressures. The maximal lengths and weights of both algal species were recorded for each season over a 12‐month period beginning with the spring of 2003. C. kondoi grew in length at a faster rate than N. aculeate, whereas the turf alga N. aculeata produced new branches from the tips of broken branches. The reproductive period of C. kondoi was between the spring and summer but the reproductive organs of N. aculeata were observed throughout the year. The algal loss rate of fresh N. aculeata to snails was low but snails had a food preference for N. aculeata when compared to C. kondoi in an artificial food experiment. These results indicate that snails may adapt to chemical compounds characteristic of N. aculeata and that the alga further reduces predation damage by its structural resistance. In conclusion, the survival strategies of C. kondoi appear to be rapid growth, seasonal sexual reproduction, and a delicately branched frond morphology that reduces stable feeding patterns of its predators plus high tissue nitrogen content, whereas the survival strategy of N. aculeata includes regenerative growth responses, structural toughness and chemical defenses while under the grazing pressure of herbivorous snails.     

Chloride channel activity of vascular smooth muscle in the spontaneous hypertensive rats

To characterize the activity of the Ca2+-activated Cl- channels in vascular smooth muscle (VSM) of the spontaneous hypertensive rats (SHR), the isolated mesenteric vascular beds and tail artery strips were preparated from SHR and Wistar rats aged 7-8 weeks. The changes in contractile response to norepinphrine (NE) were taken as an index of vascular mortion. Results showed that the contractile responses of mesenteric arteries and tail arteries to NE in SHR were significantly greater than that in Wistar rats. The inhibition magnitude of the contractile response by Ca2+-activated Cl- channel blocker, niflumic acid in SHR was significantly less than that in Wistar rats. Decreasing the extracellular Cl- concentration increased the contractile response to NE significantly, but the amplitude of enhanced contractile response in SHR was greater than that in Wistar rats. It can be concluded that NE-induced contraction was enhanced in SHR, which is partly due to an increase in Cl- efflux through the Ca2+-activated Cl- channels. The chloride channel activity may be increased in association with the elevation of blood pressure.     

Prevalence of Gymnophalloides seoi infection in coastal villages of Haenam-gun and Yeongam-gun, Republic of Korea

One coastal village in Haenam-gun and two in Yeongam-gun, Jeollanam-do were surveyed for intestinal parasite infections by fecal examination. The egg positive rates of Gymnophalloides seoi were high, 24.1% (14/58) in Haenam-gun and 9.3% (11/118) in Yeongam-gun. The egg positive rates of heterophyids, including Heterophyes nocens, and of Clonorchis sinensis were 10.3% and 6.9% in Haenam-gun, and 14.4% and 8.5% in Yeongam-gun, respectively. After praziquantel treatment and purgation, a total of 37,761 fluke specimens were recovered from 17 patients; 11 in Haenam-gun and 6 in Yeongam-gun. Gymnophalloides seoi was the most commonly recovered species, with 37,489 specimens in total (2,205 per person). Other recovered flukes included Heterophyes nocens, Stictodora fuscata, Heterophyopsis continua, Pygidiopsis summa, and undetermined species. These results indicate that the areas surveyed are new endemic foci of G. seoi.     

Molecular steps of G‐overhang generation at human telomeres and its function in chromosome end protection

Telomeric G‐overhangs are required for the formation of the protective telomere structure and telomerase action. However, the mechanism controlling G‐overhang generation at human telomeres is poorly understood. Here, we show that G‐overhangs can undergo cell cycle‐regulated changes independent of telomerase activity. G‐overhangs at lagging telomeres are lengthened in S phase and then shortened in late S/G2 because of C‐strand fill‐in, whereas the sizes of G‐overhangs at leading telomeres remain stable throughout S phase and are lengthened in G2/M. The final nucleotides at measurable C‐strands are precisely defined throughout the cell cycle, indicating that C‐strand resection is strictly regulated. We demonstrate that C‐strand fill‐in is mediated by DNA polymerase α (polα) and controlled by cyclin‐dependent kinase 1 (CDK1). Inhibition of CDK1 leads to accumulation of lengthened G‐overhangs and induces telomeric DNA damage response. Furthermore, depletion of hStn1 results in elongation of G‐overhangs and an increase in telomeric DNA damage. Our results suggest that G‐overhang generation at human telomeres is regulated by multiple tightly controlled processes and C‐strand fill‐in is under the control of polα and CDK1.