Palmitic acid methyl ester induces cardiac hypertrophy through activating the GPR receptor-mediated changes of intracellular calcium concentrations and mitochondrial functions

Myocardial hypertrophy is associated with a significant increase in intracellular Ca²⁺, which can be induced by long-chain fatty acid. Palmitic acid methyl ester (PAME), a fatty acid ester released from adipose tissue, superior cervical ganglion, and retina, has been found to have anti-inflammation, antifibrosis, and peripheral vasodilation effects. However, the effects of PAME on cardiomyocytes are still unclear. The aim of this study was to determine whether PAME could disrupt the intracellular Ca²⁺ balance, leading to cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were treated with various concentrations (10–100 μM) of PAME for 1–4 days. Cytosolic Ca²⁺ and mitochondrial Ca²⁺ concentrations were examined using Fura-2 AM and Rhod-2, respectively. After treatment with PAME for 4 days, mitochondrial Ca²⁺, an indicator of the state of mitochondrial permeability transition pore (MPTP), and cell death were monitored by flow cytometric analysis. ATP levels were detected using the ATP assay kit. Cardiomyocyte hypertrophy was analyzed by measuring the cardiac hypertrophy biomarker and cell area using quantitative real time-polymerase chain reaction, Western Blot analysis and immunofluorescence analysis. Our results show that PAME concentration- and time-dependently increased cytosolic and mitochondria Ca²⁺ through the mitochondrial calcium uniporter. Moreover, treatment with PAME for 4 days caused MPTP opening, thereby reducing ATP production and enhancing reactive oxygen species (ROS) generation, and finally led to cardiomyocyte hypertrophy. These effects caused by PAME treatment were attenuated by the G-protein coupled receptor 40 (GPR40) inhibitor. In conclusion, PAME impaired mitochondrial function, which in turn led to cardiomyocyte hypertrophy through increasing the mitochondrial Ca²⁺ levels mediated by activating the GPR40 signaling pathway.     

Membrane partitioning of peptide aggregates: coarse-grained molecular dynamics simulations

Abstract

Coarse-grained molecular dynamics (CGMD) simulation technique (MARTINI force field) is applied to monitor the aggregation of helical peptides representing the transmembrane sequence and its extension of bone marrow stromal cell antigen 2 (BST-2). One of the peptides is coupled with a protein transducing domain (PTD) of nine arginine residues (R9) at its N-terminal side as well as a peptide, pep11**, which has been shown to bind to human papilloma virus 16 (HPV16) E6 oncoprotein. A short hydrophobic stretch of the transmembrane domain (TMD) of BST-2 aggregates the fastest and inserts into a lipid membrane. An aggregate of R9-pep11** attaches to the membrane via simultaneous contact of many arginine residues. Monomers from the aggregates of the shortest of the hydrophobic TMDs dissolve into the opposing leaflet when the aggregate spans the bilayer. A ‘flipping’ of the individual monomeric peptides is not observed.

Communicated by Ramaswamy H. Sarma     

Comparison of milk protein allele frequencies in Nordic cattle breeds

Allele frequencies at four milk protein loci were studied in five modern and 17 old Nordic cattle breeds in order to reveal variants that are characteristic for these populations. The B allele of CSN3, which has been associated with improved manufacturing properties of milk, showed significantly lower frequencies in modern production breeds than in old breeds of interest for conservation purposes. Characteristic frequencies of CSN1S1 (C), CSN2 (A2) and CSN3 (B) were found in Icelandic cattle, Swedish Mountain cattle, Northern Finncattle and Western Fjord cattle, which indicate a common origin of these populations. Further comparisons of allele frequencies in old Nordic breeds suggest sorting of these breeds into two groups with a northern and southern geographic location.     

Taxonomic notes on the paper wasps of the genus Ropalidia in the Indian subcontinent (Hymenoptera: Vespidae)

The taxonomy of Ropalidia wasps in the Indian subcontinent is revised, recognizing 26 species in the subcontinent. Their diagnostic characteristics are summarized in a key to species. New synonymies proposed in the present study are: R. bicolorata shiva Das and Gupta, 1989 under R. bicolorata van der Vecht, 1962; R. colorata sordida van der Vecht, 1941 under R. colorata van der Vecht, 1941; R. rodialipa Lambert and Narendran, 2005 and R. anupama Lambert and Narendran, 2005, both under R. cyathiformis Fabricius, 1804; R. jacobsoni flavoscutellata Das and Gupta, 1989, and R. bangalorica Lambert and Narendran, 2005, both under R. jacobsoni du Buysson, 1908; R. travancorica Lambert and Narendran, 2005, under R. marginata Lepeletier, 1836; R. sridharani Lambert and Narendran, 2005, under R. rufocollaris Cameron, 1900; Ropalidia rufoplagiata nursei van der Vecht, 1941 under R. rufoplagiata Cameron, 1905; Icaria lugubris Smith, 1858, under R. sumatrae Weber, 1801; and a revised synonymy is Icaria pendula Smith, 1857, under R. variegata Smith, 1852. The new replacement name Ropalidia kasaragodensis Lambert and Narendran is proposed for R. indica Lambert and Narendran, 2005, non van der Vecht, 1941.     

Possible circulation of H5N1 avian influenza viruses in healthy ducks on farms in northern Vietnam

To estimate the prevalence of influenza A subtype H5N1 viruses among domestic ducks in the period between October and November 2006 when H5N1 outbreaks had been absent, 1106 healthy ducks raised in northern Vietnam were collected. Inoculation of all throat and cloacae samples into embryonated eggs resulted in the isolation of subtype H3N8 in 13 ducks, but not H5N1 viruses. Serological analyses demonstrated that five ducks (0.45%) solely developed H5N1 subtype-specific hemagglutinin-inhibiting and neuraminidase-inhibiting antibodies together with anti-non-structural protein 1 antibodies. The results suggested that the ducks were naturally infected with H5N1 viruses when obvious H5N1 outbreaks were absent.     

An Application of Renewal Theory to Contraceptive Follow-up Studies,Exemplified by an Intrauterine Device Study

Contraceptive practice consists of a series of recurrent events of use and nonuse. Application of the life table technique for analysis of multiple-segment contraceptive usage is not entirely satisfactory. In this paper the renewal process approach is applied to the results of contraceptive follow-up studies involving all segments of use. By means of this model, it is possible to estimate the proportion of current users, the average duration of actual use, and the average number of segments used by the acceptors. The practical importance of these parameters for the evaluation of family planning programs is considered.