Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis

Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult stage of this liver fluke in recent years has advanced our understanding of the pathological interplay between this parasite and its hosts. However, no developmental gene expression profiles of C. sinensis have been published. In this study, we generated gene expression profiles of three developmental stages of C. sinensis by analyzing expressed sequence tags (ESTs). Complementary DNA libraries were constructed from the adult, metacercaria, and egg developmental stages of C. sinensis. A total of 52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST sequences, and then these assemblies were further categorized into groups according to biological functions and developmental stages. Most of the genes that were differentially expressed in the different stages were consistent with the biological and physical features of the particular developmental stage; high energy metabolism, motility and reproduction genes were differentially expressed in adults, minimal metabolism and final host adaptation genes were differentially expressed in metacercariae, and embryonic genes were differentially expressed in eggs. The higher expression of glucose transporters, proteases, and antioxidant enzymes in the adults accounts for active uptake of nutrients and defense against host immune attacks. The types of ion channels present in C. sinensis are consistent with its parasitic nature and phylogenetic placement in the tree of life. We anticipate that the transcriptomic information on essential regulators of development, bile chemotaxis, and physico-metabolic pathways in C. sinensis that presented in this study will guide further studies to identify novel drug targets and diagnostic antigens

International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease

Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. Results: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0–2 SNPs) with the common ancestor dated around 2017. Conclusion: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination

The role of sediment organic matter composition in larval habitat selection by the polychaete Capitella sp. I

The role of sediment organic matter composition in larval habitat selection by the polychaete Capitella sp. I was investigated using a still water multiple-choice experiment. Specifically, the following question was addressed: what are the roles of sediment labile organic compounds in larval habitat selection? A replicated Latin-square design was used to test larval preferences among sediments collected from five sites (TLC-Tung Lung Chau; VHE-Victoria Harbor east; VH-Victoria Harbor; VHW-Victoria Harbor west; PC-Peng Chau) in the vicinity of Victoria Harbor, Hong Kong. Although mean grain size was not different among sites, water content and the total organic matter were higher in VH Mud but were similar among other sites. Carbohydrate, lipid, and biopolymeric fractions followed the same trend. According to protein content, sites were ranked as: VH > VHW > TLC = VHE > PC. PC Mud had the highest carbohydrate/protein ratio, due to low concentration of protein. According to larval preference, sites were ranked as: TLC = VH = VHW = VHE > PC. Our study shows a precise relationship between sediment biochemical properties and larval habitat selection. Larvae tend to choose sediments with low carbohydrate/protein ratio. Results suggest that types of sediment organic matter may play more important role in the larval habitat selection process of Capitella sp. I than concentration of organic matter alone. © 2005 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

Spatio-temporal variation in sediment biochemistry alters larval habitat selection and juvenile performance in the polychaete Capitella sp. I

The aim of the present study was to understand how larvae and juveniles of the opportunistic polychaete Capitella sp. I respond to natural sediments with varying biochemical properties. Muddy sediments of a similar particle size spectrum were collected from 5 sites in Hong Kong along a pollution gradient of domestic sewage on 4 sampling occasions in both wet and dry seasons. The sediments were used to study the influence of organic matter quantity and composition (i.e. total organic carbon [TOC], total nitrogen [TN], chlorophyll a, biopolymeric carbon and enzymatically hydrolysable amino acid contents) on larval metamorphosis (i.e. habitat selection) and juvenile performance (i.e. growth and survivorship). Organic matter quantity and composition varied with sampling date and site. Still water multiple-choice experiments showed that larval choice at settlement varied with spatial and temporal variations in sediment biochemical properties. A series of experiments in the study also showed that both the quantity and the composition of organic matter affect the attractiveness of substrates to larvae and appear to play a key role in determining larval behavior at the time of settlement. Further laboratory experiments showed that larvae did not choose to settle on sediments from sites where juvenile growth was poor and mortality was higher. Our field data indicated that both larval metamorphosis and juvenile performance patterns observed in this laboratory study partially corroborate data on the abundance of adult Capitella spp. in the field. Overall, this study suggests that the field distribution of Capitella sp. I, and consequently species composition in a community, could be determined by the habitat selection by larvae and early juvenile performance. © Inter-Research 2006.link_to_subscribed_fulltex

Germline APOBEC3B deletion is associated with breast cancer risk in an Asian multi-ethnic cohort and with immune cell presentation

Background: APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system. Methods: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT. Results: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values < 0.05). Analysis of breast cancers from METABRIC revealed breast cancers from APOBEC3B deletion carriers to have significantly higher abundance of tumour-infiltrating immune cells (P < 0.001). Conclusions: Taken together, our data suggests that tumour-infiltrating immune cells may be an important feature of breast cancers arising in women with APOBEC3B germline deletion, and that this may be of particular interest in Asian women where the germline deletion is more common

Germline APOBEC3B deletion is associated with breast cancer risk in an Asian multi-ethnic cohort and with immune cell presentation

Background: APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system. Methods: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT. Results: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values < 0.05). Analysis of breast cancers from METABRIC revealed breast cancers from APOBEC3B deletion carriers to have significantly higher abundance of tumour-infiltrating immune cells (P Conclusions: Taken together, our data suggests that tumour-infiltrating immune cells may be an important feature of breast cancers arising in women with APOBEC3B germline deletion, and that this may be of particular interest in Asian women where the germline deletion is more common

Target-selective GABAergic control of entorhinal cortex output

The medial entorhinal cortex (MEC) is a major center for spatial navigation and memory. We demonstrate that cannabinoid type-1 receptor-expressing GABAergic basket cells selectively innervate principal cells in layer II of the rat MEC that project outside the hippocampus, but avoid neighboring cells giving rise to the perforant pathway to the dentate gyrus. These results show that the organization of GABAergic microcircuits reflects the long-distance axonal targets of principal neurons. Keywords interneuron; cannabinoid; spatial navigation; grid cell; dentate gyrus; GABA Layer II of the medial entorhinal cortex (MEClayerII) is a key part of a distributed network for spatial navigation and memory processing1–4, and it gives rise to the associational glutamatergic pathway known as the perforant path that terminates in the molecular layer of the dentate gyrus5,6. In neocortical and hippocampal networks, a major regulator of principal neurons is the cholecystokinin and cannabinoid type-1 receptor (CB1R)-expressing basket cells (CCKBCs)7. It is generally assumed that basket cells provide perisomatic inhibition t