Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B viruspositive HCC through the generation of a large set of 5-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes͞ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes͞ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function͞differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC͞noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-␤-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. Knowledge of the genome of this parasite should improve understanding of schistosome-host interactions, biomedical aspects of schistosomiasis and invertebrate evolution. We assigned 43,707 expressed sequence tags (ESTs) derived from adult S. japonicum and their eggs to 13,131 gene clusters. Of these, 35% shared no similarity with known genes and 75% had not been reported previously in schistosomes. Notably, S. japonicum encoded mammalian-like receptors for insulin, progesterone, cytokines and neuropeptides, suggesting that host hormones, or endogenous parasite homologs, could orchestrate schistosome development and maturation and that schistosomes modulate anti-parasite immune responses through inhibitors, molecular mimicry and other evasion strategies.

Schistosomes are the causative agents of schistosomiasis, one of the most prevalent and serious of the parasitic diseases that currently infects ϳ200 million people worldwide. Schistosome excretory/secretory (ES) proteins have been shown to play important roles in modulating mammalian host immune systems. In our current study, we performed a global proteomics identification of the ES proteins from adult worms of Schistosoma japonicum, one of the three major schistosome species. Our results unambiguously identified 101 proteins, including 53 putatively secreted proteins. By quantitative analysis, we revealed fatty acid-binding protein as a major constituent of the in vitro ES proteome. Strikingly the heat shock proteins HSP70s, HSP90, and HSP97 constituted the largest protein family in the ES proteome, implying a central role for these proteins in immunomodulation in the hostparasite relationship. Other important S. japonicum ES proteins included actins, 14-3-3, aminopeptidase, enolase, and glyceraldehyde-3-phosphate dehydrogenase, some of which have been considered as viable vaccine candidates and therapeutic targets. A comparison with previous studies suggests that 48.5% of S. japonicum ES proteins are common to other parasite ES products, indicating that the molecular mechanisms involved in evading the host immune response may be conserved across different parasites. Interestingly seven host proteins, including antimicrobial protein CAP18, immunoglobulins, and a complement component, were identified among in vitro S. japonicum ES products likely originating from the schistosome tegument or gut, indicating that host innate and acquired immune systems could defend against schistosome invasion. Our present study represents the first attempt at profiling S. japonicum ES proteins, provides an insight into host-parasite interactions, and establishes a resource for the devel-

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

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Growth factors such as brain-derived neurotrophic factor (BDNF) are widely used in the recovery of spinal cord injury (SCI) for promoting axonal regeneration or improving neuron survival. However, the lack of efficient delivery approaches limits their clinical applications. In this study, we constructed an efficient delivery system including collagen-binding BDNF and linear ordered collagen scaffolds (LOCS). A collagen-binding domain (CBD) was utilized to construct collagen-targeting BDNF (CBD-BDNF) to allow its specific binding to the collagen. In vitro activity assay showed that CBD-BDNF had similar bioactivity in neurite outgrowth of dorsal root ganglia and the survival of PC12 cells. CBD-BDNF was shown to have specific binding activity to collagen. Using the rat hemisection SCI model, we found that LOCS loaded with CBD-BDNF significantly improved the SCI recovery evaluated by the Basso, Beattie, and Bresnahan scale and immunohistochemical staining with anti-neurofilament antibody. Thus, this targeting drug delivery system consisting of CBD-BDNF and LOCS could be an effective strategy for the repair of SCI.

Tropical diseases remain a major cause of morbidity and mortality in developing countries. Although combined health efforts brought about significant improvements over the past 20 years, communities in resource-constrained settings lack the means of strengthening their environment in directions that would provide less favourable conditions for pathogens. Still, the impact of infectious diseases is declining worldwide along with progress made regarding responses to basic health problems and improving health services delivery to the most vulnerable populations. The London Declaration on Neglected Tropical Diseases (NTDs), initiated by the World Health Organization’s NTD roadmap, set out the path towards control and eventual elimination of several tropical diseases by 2020, providing an impetus for local and regional disease elimination programmes. Tropical diseases are often patchy and erratic, and there are differing priorities in resources-limited and endemic countries at various levels of their public health systems. In order to identify and prioritize strategic research on elimination of tropical diseases, the ‘First Forum on Surveillance-Response System Leading to Tropical Diseases Elimination’ was convened in Shanghai in June 2012. Current strategies and the NTD roadmap were reviewed, followed by discussions on how to identify and critically examine prevailing challenges and opportunities, including inter-sectoral collaboration and approaches for elimination of several infectious, tropical diseases. A priority research agenda within a ‘One Health-One World’ frame of global health was developed, including (i) the establishment of a platform for resource-sharing and effective surveillance-response systems for Asia Pacific and Africa with an initial focus on elimination of lymphatic filariasis, malaria and schistosomiasis; (ii) development of new strategies, tools and approaches, such as improved diagnostics and antimalarial therapies; (iii) rigorous validation of surveillance-response systems; and (iv) designing pilot studies to transfer Chinese experiences of successful surveillance-response systems to endemic countries with limited resources.