The mitochondrial genome of Baylisascaris procyonis

Background

Baylisascaris procyonis (Nematoda: Ascaridida), an intestinal nematode of raccoons, is emerging as an important helminthic zoonosis due to serious or fatal larval migrans in animals and humans. Despite its significant veterinary and public health impact, the epidemiology, molecular ecology and population genetics of this parasite remain largely unexplored. Mitochondrial (mt) genomes can provide a foundation for investigations in these areas and assist in the diagnosis and control of B. procyonis. In this study, the first complete mt genome sequence of B. procyonis was determined using a polymerase chain reaction (PCR)-based primer-walking strategy.

Methodology/Principal Findings

The circular mt genome (14781 bp) of B. procyonis contained 12 protein-coding, 22 transfer RNA and 2 ribosomal RNA genes congruent with other chromadorean nematodes. Interestingly, the B. procyonis mtDNA featured an extremely long AT-rich region (1375 bp) and a high number of intergenic spacers (17), making it unique compared with other secernentean nematodes characterized to date. Additionally, the entire genome displayed notable levels of AT skew and GC skew. Based on pairwise comparisons and sliding window analysis of mt genes among the available 11 Ascaridida mtDNAs, new primer pairs were designed to amplify specific short fragments of the genes cytb (548 bp fragment) and rrnL (200 bp fragment) in the B. procyonis mtDNA, and tested as possible alternatives to existing mt molecular beacons for Ascaridida. Finally, phylogenetic analysis of mtDNAs provided novel estimates of the interrelationships of Baylisasaris and Ascaridida.

Conclusions/Significance

The complete mt genome sequence of B. procyonis sequenced here should contribute to molecular diagnostic methods, epidemiological investigations and ecological studies of B. procyonis and other related ascaridoids. The information will be important in refining the phylogenetic relationships within the order Ascaridida and enriching the resource of markers for systematic, population genetic and evolutionary biological studies of parasitic nematodes of socio-economic importance.     

Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo

Background

Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms.

Methodology/Principal Findings

We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼−11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo.

Conclusions/Significance

In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.     

Endogenous synthesis of n-3 polyunsaturated fatty acids in Fat-1 mice is associated with increased mammary gland and liver syndecan-1

Long chain n-3 PUFA have been shown to have chemopreventive properties against breast cancer through various mechanisms. One pathway, studied in human breast cancer cell lines, involves upregulation of the proteoglycan, syndecan-1 (SDC-1) by n-3 PUFA-enriched LDL. Using Fat-1 mice that are able to convert n-6 to n-3 PUFA, we tested whether SDC-1 level in vivo is elevated in mammary glands due to endogenously synthesized rather than LDL-derived n-3 PUFA. Female Fat-1 and wild type (wt) mice were fed an n-6 PUFA- enriched diet for 7 weeks. Fatty acid analysis of plasma lipoproteins showed that total n-6 PUFA reflected dietary intake similarly in both genotypes (VLDL, 36.2±2.2 and 40.9±3.9; LDL, 49.0±3.3 and 48.1±2.0; HDL, 54.6±1.2 and 58.2±1.3, mean ± SEM percent of total fatty acids for Fat-1 and wt animals respectively). Lipoprotein percent n-3 PUFA was also similar between groups. However, phospholipids and triglycerides extracted from mammary and liver tissues demonstrated significantly higher n-3 PUFA and a corresponding decrease in the ratio n-6/n-3 PUFA in Fat-1 compared to wt mice. This was accompanied by higher SDC-1 in mammary glands and livers of Fat-1 mice, thus demonstrating that endogenously synthesized n-3 PUFA may upregulate SDC-1 in the presence of high dietary n-6 PUFA.     

PAX6 haplotypes are associated with high myopia in Han chinese

Background

The paired box 6 (PAX6) gene is considered as a master gene for eye development. Linkage of myopia to the PAX6 region on chromosome 11p13 was shown in several studies, but the results for association between myopia and PAX6 were inconsistent so far.

Methodology/Principal Findings

We genotyped 16 single nucleotide polymorphisms (SNPs) in the PAX6 gene and its regulatory regions in an initial study for 300 high myopia cases and 300 controls (Group 1), and successfully replicated the positive results with another independent group of 299 high myopia cases and 299 controls (Group 2). Five SNPs were genotyped in the replication study. The spherical equivalent of subjects with high myopia was ≤−8.0 dioptres. The PLINK package was used for genetic data analysis. No association was found between each of the SNPs and high myopia. However, exhaustive sliding-window haplotype analysis highlighted an important role for rs12421026 because haplotypes containing this SNP were found to be associated with high myopia. The most significant results were given by the 4-SNP haplotype window consisting of rs2071754, rs3026393, rs1506 and rs12421026 (P = 3.54×10⁻¹⁰, 4.06×10⁻¹¹ and 1.56×10⁻¹⁸ for Group 1, Group 2 and Combined Group, respectively) and the 3-SNP haplotype window composed of rs3026393, rs1506 and rs12421026 (P = 5.48×10⁻¹⁰, 7.93×10⁻¹² and 6.28×10⁻²³ for the three respective groups). The results remained significant after correction for multiple comparisons by permutations. The associated haplotyes found in a previous study were also successfully replicated in this study.

Conclusions/Significance

PAX6 haplotypes are associated with susceptibility to the development of high myopia in Chinese. The PAX6 locus plays a role in high myopia.     

Evidence of successful recruitment of non-native pink salmon Oncorhynchus gorbuscha in Iceland

In mid-May 2022, pink salmon Oncorhynchus gorbuscha smolts were caught in the rivers Botnsá, Grímsá, and Langá in Iceland. This observation provides the first evidence of successful spawning and the completion of the freshwater phase of the life cycle in Icelandic rivers. It is the most western record of O. gorbuscha smolts in Europe, further west than Russia, Norway, and the UK. Smolts originating from Iceland potentially support the recruitment of this species in the North Atlantic and may lead to the establishment of a self-sustaining population in Iceland.     

Trade-off between mobility and fitness in Cydia pomonella L. (Lepidoptera: Tortricidae)

Abstract.  1. The codling moth Cydia pomonella , one of the most important pest insects of apple fruit orchards worldwide, is regarded as a 'sedentary' insect, but the natural populations consist of both mobile and sedentary genotypes that display different dispersal capacity in the field. The current study investigated whether there is a fitness consequence of being mobile in this species by comparing two strains with contrasting levels of mobility obtained through bi-directional selection.
2. Female moths of the sedentary strain were significantly larger, laid more eggs during their lifespan, and both male and female moths of this strain lived longer, when compared with the mobile strain.
3. The age-specific fecundity of female moths from the sedentary strain was significantly greater, in particular between 3 and 5 days after emergence when the peaks of both oviposition and flight capacity occur, relative to the mobile moths, thereby leading to a greater reproductive function.
4. These differences resulted in different demographic parameters between the two strains. The sedentary strain had a significantly greater net reproductive rate ( R _o ) and a higher intrinsic rate of natural increase ( r _m ), although the generation time ( T ) was similar, hence requiring a shorter time to double the population size, in comparison to the mobile strain.
5. This study provides empirical evidence for the cost of being mobile in C. pomonella . Trade-offs between mobility and fitness might have contributed to the existence of genetic variance for dispersal behaviour in the natural populations and the maintenance of relative sedentariness in the species.     

Binding of 3H-gossypol in organelles of cultured bovine luteal cells.

Gossypol is an antifertility agent which inhibits steroidogenesis in both sexes. The present study investigated the binding of gossypol in organelles of cultured bovine luteal cell to elucidate its inhibitory site of action in steroid biosynthesis. Cultured bovine luteal cells were incubated with 3H-gossypol (4.3 or 2.15 microM) for 3 hours. At the end of treatment, cultured bovine luteal cells were harvested, homogenized and centrifuged for organelle preparation. The radioactivity of gossypol was measured in each subcellular fraction. The cell membrane fraction has the highest binding capacity for gossypol, and the majority of gossypol was located in the particulate fractions. Results of the present study provide information in understanding the regulatory mechanism of gossypol on antisteroidogenic and/or toxic effects in cultured bovine luteal cells.