AZI23'UTR Is a New SLC6A3 Downregulator Associated with an Epistatic Protection Against Substance Use Disorders

Regulated activity of SLC6A3, which encodes the human dopamine transporter (DAT), contributes to diseases such as substance abuse disorders (SUDs); however, the exact transcription mechanism remains poorly understood. Here, we used a common genetic variant of the gene, intron 1 DNP1B sequence, as bait to screen and clone a new transcriptional activity, AZI23'UTR, for SLC6A3. AZI23'UTR is a 3' untranslated region (3'UTR) of the human 5-Azacytidine Induced 2 gene (AZI2) but appeared to be transcribed independently of AZI2. Found to be present in both human cell nuclei and dopamine neurons, this RNA was shown to downregulate promoter activity through a variant-dependent mechanism in vitro. Both reduced RNA density ratio of AZI23'UTR/AZI2 and increased DAT mRNA levels were found in ethanol-naive alcohol-preferring rats. Secondary analysis of dbGaP GWAS datasets (Genome-Wide Association Studies based on the database of Genotypes and Phenotypes) revealed significant interactions between regions upstream of AZI23'UTR and SLC6A3 in SUDs. Jointly, our data suggest that AZI23'UTR confers variant-dependent transcriptional regulation of SLC6A3, a potential risk factor for SUDs

Multi-Host Model-Based Identification of \u3ci\u3eArmillifer agkistrodontis\u3c/i\u3e (Pentastomida), a New Zoonotic Parasite from China

Background: Pentastomiasis is a rare parasitic infection of humans. Pentastomids are dioecious obligate parasites requiring multiple hosts to complete their life cycle. Despite their worm-like appearance, they are commonly placed into a separate sub-class of the subphylum Crustacea, phylum Arthropoda. However, their systematic position is not uncontested and historically, they have been considered as a separate phylum. Methodology/Principal Findings: An appraisal of Armillifer agkistrodontis was performed in terms of morphology and genetic identification after its lifecycle had been established in a multi-host model, that is, mice and rats as intermediate hosts, and snakes (Agkistrodon acutus and Python molurus) as definitive hosts. Different stages of the parasite, including eggs, larvae and adults, were isolated and examined morphologically using light and electron microscopes. Phylogenetic and cluster analysis were also undertaken, focusing on the 18S rRNA and the Cox1 gene. The time for lifecycle completion was about 14 months, including 4 months for the development of eggs to infectious larvae in the intermediate host and 10 months for infectious larvae to mature in the final host. The main morphological difference between A. armillatus and Linguatula serrata is the number of abdominal annuli. Based on the 18S rRNA sequence, the shortest hereditary distance was found between A. agkistrodontis and Raillietiella spp. The highest degree of homology in the Cox 1 nucleic acid sequences and predicted amino acid sequences was found between A. agkistrodontis and A. armillatus. Conclusion: This is the first time that a multi-host model of the entire lifecycle of A. agkistrodontis has been established. Morphologic and genetic analyses supported the notion that pentastomids should be placed into the phylum Arthropoda

Multi-host Model-Based Identification of Armillifer agkistrodontis (Pentastomida), a New Zoonotic Parasite from China

Little information is currently available on the lifecycle and morphology of pentastomids, a new zoonotic parasite in China. The lifecycle of Armillifer agkistrodontis was established in multiple hosts, i.e., an intermediate host and a definitive host, and the parasite examined in terms of morphology and genetic relationship with other species. The time required for the completion of an entire lifecycle was about 14 months. The main morphological difference between A. armillatus and L. serrata is the number of abdominal annuli. The genetic data supported the notion that pentastomids belong to the phylum Arthropoda. Based on the 18S rRNA sequence, the shortest hereditary distance was found between A. agkistrodontis and Raillietiella spp. The highest similarity in the Cox 1 nucleic acid sequences was found between A. agkistrodontis and A. armillatus. The established multi-host model provides a possible approach to confirm suspected infections and offers an opportunity to further study this parasite

Negative and Positive Lateral Shift of a Light Beam Reflected from a Grounded Slab

We consider the lateral shift of a light beam reflecting from a dielectric slab backed by a metal. It is found that the lateral shift of the reflected beam can be negative while the intensity of reflected beam is almost equal to the incident one under a certain condition. The explanation for the negativity of the lateral shift is given in terms of the interference of the reflected waves from the two interfaces. It is also shown that the lateral shift can be enhanced or suppressed under some other conditions. The numerical calculation on the lateral shift for a realistic Gaussian-shaped beam confirms our theoretical prediction.Comment: 8pages,4 figure

Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet

<p>Abstract</p> <p>Background</p> <p>The hypocholesterolemic effects of lactic acid bacteria (LAB) have now become an area of great interest and controversy for many scientists. In this study, we evaluated the effects of <it>Lactobacillus plantarum </it>9-41-A and <it>Lactobacillus fermentum </it>M1-16 on body weight, lipid metabolism and intestinal microflora of rats fed a high-cholesterol diet.</p> <p>Methods</p> <p>Forty rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The LAB-treated groups received the high-cholesterol diet supplemented with <it>Lactobacillus plantarum </it>9-41-A or <it>Lactobacillus fermentum </it>M1-16. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum and liver cholesterol and lipid levels, and fecal cholesterol and bile acid concentrations were measured. Liver lipid deposition and adipocyte size were evaluated histologically.</p> <p>Results</p> <p>Compared with rats fed a high-cholesterol diet but without LAB supplementation, serum total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in LAB-treated rats (p < 0.05), with no significant change in high-density lipoprotein cholesterol levels. Hepatic cholesterol and triglyceride levels and liver lipid deposition were significantly decreased in the LAB-treated groups (p < 0.05). Accordingly, both fecal cholesterol and bile acids levels were significantly increased after LAB administration (p < 0.05). Intestinal <it>Lactobacillus </it>and <it>Bifidobacterium </it>colonies were increased while <it>Escherichia coli </it>colonies were decreased in the LAB-treated groups. Fecal water content was higher in the LAB-treated groups. Compared with rats fed a high-cholesterol diet, administration of <it>Lactobacillus plantarum </it>9-41-A resulted in decreases in the body weight gain, liver and fat pad weight, and adipocytes size (p < 0.05).</p> <p>Conclusions</p> <p>This study suggests that LAB supplementation has hypocholesterolemic effects in rats fed a high-cholesterol diet. The ability to lower serum cholesterol varies among LAB strains. Our strains might be able to improve the intestinal microbial balance and potentially improve intestinal transit time. Although the mechanism is largely unknown, <it>L. plantarum </it>9-41-A may play a role in fat metabolism.</p