Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. Chromosome translocation t(1;3) and frequent loss of heterogeneity on short arms of chromosome 3 and 9 have been reported to be associated with NPC, and a genome-wide scan identified an NPC susceptibility locus on chromosome 4p15.1-q12 recently. In our study, we collected samples from 18 families at high risk of NPC from the Hunan province in southern China, genotyped with a panel of polymorphic markers on short arms of chromosomes 3, 9, and 4p15.1-q12. A locus on 3p21 was identified to link to NPC with a maximum logarithm of odds for linkage score of 4.18. Fine mapping located the locus to a 13.6-cM region on 3p21.31-21.2, where a tumor suppressor gene cluster resided. Our findings identified a novel locus for NPC and provided a map location for susceptibility genes candidates. In contrast to a recent study, no significant evidence for NPC linkage to chromosomes 4 and 9 was observed.

Schistosomiasis japonica is an endemic, zoonotic disease of major public health importance in China where water buffaloes account for approximately 75% of disease transmission. Interventions that reduce schistosome infection in water buffaloes will enhance their health simultaneously reducing disease transmission to humans. While chemotherapy has proved successful, it requires continued time consuming and expensive mass treatments. A more sustainable option would be development of vaccines that reduce transmission of S. japonicum from bovines to replace bovine chemotherapy. We performed two randomized double blind trials in water buffaloes to determine if DNA vaccines encoding triose-phosphate isomerase (SjCTPI), or the tetraspanin 23 kDa integral membrane protein (SjC23), alone or fused to bovine heat shock protein 70 (Hsp70) could induce a level of immunity conducive to long-term sustainable control. Groups of water buffaloes (15/group) received three intramuscular injections, 4 weeks apart. Booster immunizations were co-administered with a plasmid DNA encoding IL-12. Four weeks after the last injection, water buffaloes were challenged with 1000 cercariae, and vaccine efficacy analyzed 8 weeks later. Water buffaloes vaccinated with SjCTPI-Hsp70 or SjCTPI plasmids had worm burdens reduced by 51.2% and 41.5%, respectively. Importantly, fecal miracidial hatching was reduced by 52.1% and 33.2% respectively compared to control vaccinated water buffaloes. Vaccination with SjC23-Hsp70 and SjC23 plasmids reduced worm burdens by 50.9% and 45.5%, respectively, and fecal miracidial hatching by 52.0% and 47.4%. A mathematical model of schistosome transmission predicts that schistosome vaccines capable of reducing water buffaloes' fecal egg output by 45%, alone or in conjunction with praziquantel treatment, will lead to a significant reduction in transmission of schistosomiasis. Both DNA vaccines tested here exceed this hypothetical level. Indeed, mathematical modeling of SjCTPI-Hsp70 and SjC23-Hsp70 alone and in conjunction with human chemotherapy showed a significant reduction in transmission almost to the point of elimination.

Cyanobacteria are oxygenic photosynthetic prokaryotes that play important roles in the global carbon cycle. Recently, engineered cyanobacteria capable of producing various small molecules from CO2 have been developed. However, cyanobacteria are seldom considered as factories for producing proteins, mainly because of the lack of efficient strong promoters. Here, we report the discovery and verification of a super-strong promoter Pcpc560, which contains two predicted promoters and 14 predicted transcription factor binding sites (TFBSs). Using Pcpc560, functional proteins were produced at a level of up to 15% of total soluble protein in the cyanobacterium Synechocystis sp. 6803, a level comparable to that produced in Escherichia coli. We demonstrated that the presence of multiple TFBSs in Pcpc560 is crucial for its promoter strength. Genetically transformable cyanobacteria neither have endotoxins nor form inclusion bodies; therefore, Pcpc560 opens the possibility to use cyanobacteria as alternative hosts for producing heterogeneous proteins from CO2 and inorganic nutrients.

Bromodomain is a 110 amino acid domain. It is evolutionally conserved and is found in proteins strongly implicated in signal-dependent transcriptional regulation. BRD7 is a novel bromodomain gene and it is downexpressed in nasopharyngeal carcinoma (NPC) biopsies and cell lines; its function is poorly understood. In the present study, tet-on inducible expression system was used to investigate the role of BRD7 in cell growth and cell cycle progression. We found that ectopic expression of BRD7 in NPC cells inhibited cell growth and cell cycle progression from G1 to S. We further performed cell cycle cDNA array to screen potential transcriptional targets of BRD7 in cell cycle. Thirteen important signaling molecules, mainly implicated in ras/MEK/ERK and Rb/E2F pathways, were differentially expressed by induction of BRD7. Moreover, we observed that BRD7 could regulate the promoter activity of E2F3, one of its targets. Taken together, the present study indicated that BRD7 inhibited G1-S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathways and suggested that BRD7 may present a promising candidate of NPC trade mark associated tumor suppressor gene.