Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer

<p>Abstract</p> <p>Background/Aim</p> <p>To explore the therapeutic effects of thymidine kinase (TK) expressed by enhanced vector pGL3-basic- hTERTp-TK-EGFP-CMV driven by human telomerase reverse transcriptase promoter (hTERTp) as well as cytomegalovirus immediate early promoter enhancer (CMV).</p> <p>Materials/Methods</p> <p>Enhanced TK-EGFP expression was confirmed by fluorescent microscopy, real time PCR and telomerase activity. Its effects were examined by survival of tumor cells NPC 5-8F and MCF-7, index of xenograft implanted in nude mice and histology.</p> <p>Results</p> <p>Compared with non-enhanced vector pGL3-basic-TK-hTERTp-EGFP, TK expressed by the enhanced vector significantly decreased NPC 5-8F and MCF-7 cell survival rates after ganciclovir (GCV) treatment (p < 0.001) and tumor progress in nude mice with NPC xenograft and treated with GCV, without obvious toxicity to mouse liver and kidney.</p> <p>Conclusion</p> <p>The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.</p

Multiple evolutionary origins of Trypanosoma evansi in Kenya

Trypanosoma evansi is the parasite causing surra, a form of trypanosomiasis in camels and other livestock, and a serious economic burden in Kenya and many other parts of the world. Trypanosoma evansi transmission can be sustained mechanically by tabanid and Stomoxys biting flies, whereas the closely related African trypanosomes T. brucei brucei and T. b. rhodesiense require cyclical development in tsetse flies (genus Glossina) for transmission. In this study, we investigated the evolutionary origins of T. evansi. We used 15 polymorphic microsatellites to quantify levels and patterns of genetic diversity among 41 T. evansi isolates and 66 isolates of T. b. brucei (n = 51) and T. b. rhodesiense (n = 15), including many from Kenya, a region where T. evansi may have evolved from T. brucei. We found that T. evansi strains belong to at least two distinct T. brucei genetic units and contain genetic diversity that is similar to that in T. brucei strains. Results indicated that the 41 T. evansi isolates originated from multiple T. brucei strains from different genetic backgrounds, implying independent origins of T. evansi from T. brucei strains. This surprising finding further suggested that the acquisition of the ability of T. evansi to be transmitted mechanically, and thus the ability to escape the obligate link with the African tsetse fly vector, has occurred repeatedly. These findings, if confirmed, have epidemiological implications, as T. brucei strains from different genetic backgrounds can become either causative agents of a dangerous, cosmopolitan livestock disease or of a lethal human disease, like for T. b. rhodesiense

LRRK2 at the interface of autophagosomes, endosomes and lysosomes

Over the past 20 years, substantial progress has been made in identifying the underlying genetics of Parkinson’s disease (PD). Of the known genes, LRRK2 is a major genetic contributor to PD. However, the exact function of LRRK2 remains to be elucidated. In this review, we discuss how familial forms of PD have led us to hypothesize that alterations in endomembrane trafficking play a role in the pathobiology of PD. We will discuss the major observations that have been made to elucidate the role of LRRK2 in particular, including LRRK2 animal models and high-throughput proteomics approaches. Taken together, these studies strongly support a role of LRRK2 in vesicular dynamics. We also propose that targeting these pathways may not only be beneficial for developing therapeutics for LRRK2-driven PD, but also for other familial and sporadic cases

Seasonal Dynamics of Mobile Carbon Supply in Quercus aquifolioides at the Upper Elevational Limit

Many studies have tried to explain the physiological mechanisms of the alpine treeline phenomenon, but the debate on the alpine treeline formation remains controversial due to opposite results from different studies. The present study explored the carbon-physiology of an alpine shrub species (Quercus aquifolioides) grown at its upper elevational limit compared to lower elevations, to test whether the elevational limit of alpine shrubs (<3 m in height) are determined by carbon limitation or growth limitation. We studied the seasonal variations in non-structural carbohydrate (NSC) and its pool size in Q. aquifolioides grown at 3000 m, 3500 m, and at its elevational limit of 3950 m above sea level (a.s.l.) on Zheduo Mt., SW China. The tissue NSC concentrations along the elevational gradient varied significantly with season, reflecting the season-dependent carbon balance. The NSC levels in tissues were lowest at the beginning of the growing season, indicating that plants used the winter reserve storage for re-growth in the early spring. During the growing season, plants grown at the elevational limit did not show lower NSC concentrations compared to plants at lower elevations, but during the winter season, storage tissues, especially roots, had significantly lower NSC concentrations in plants at the elevational limit compared to lower elevations. The present results suggest the significance of winter reserve in storage tissues, which may determine the winter survival and early-spring re-growth of Q. aquifolioides shrubs at high elevation, leading to the formation of the uppermost distribution limit. This result is consistent with a recent hypothesis for the alpine treeline formation

Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay

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Measurement of electron antineutrino oscillation based on 1230 days of operation of the Daya Bay experiment

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Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment

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Improved measurement of the reactor antineutrino flux and spectrum at Daya Bay

published_or_final_versio