Changes in Histamine Receptors (H1, H2, and H3) Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation

Vestibular compensation is the process of behavioral recovery following peripheral vestibular lesion. In clinics, the histaminergic medicine is the most widely prescribed for the treatment of vertigo and motion sickness, however, the molecular mechanisms by which histamine modulates vestibular function remain unclear. During recovery from the lesion, the modulation of histamine receptors in the medial vestibular nucleus (MVN) and the flocculus may play an important role. Here with the means of quantitative real-time PCR, western blotting and immunohistochemistry, we studied the expression of histamine receptors (H1, H2, and H3) in the bilateral MVN and the flocculus of rats on the 1st, 3rd, and 7th day following unilateral labyrinthectomy (UL). Our results have shown that on the ipsi-lesional flocculus the H1, H2 and H3 receptors mRNA and the protein increased significantly on the 1st and 3rd day, with compare of sham controls and as well the contralateral side of UL. However, on the 7th day after UL, this expression returned to basal levels. Furthermore, elevated mRNA and protein levels of H1, H2 and H3 receptors were observed in the ipsi-lesional MVN on the 1st day after UL compared with sham controls and as well the contralateral side of UL. However, this asymmetric expression was absent by the 3rd post-UL. Our findings suggest that the upregulation of histamine receptors in the MVN and the flocculus may contribute to rebalancing the spontaneous discharge in bilateral MVN neurons during vestibular compensation.     

从国家自然科学基金项目资助看植物科学态势

通过对2010-2015年度国家自然科学基金委员会生命科学部植物学学科资助的各类项目进行统计分析,总结了植物学学科资助的整体概况,详细分析了各类科学基金项目的资助特点、在不同分支学科和领域中的分布以及获资助排名前列的依托单位,并展望了我国未来植物学学科的发展趋势。     

Potential impacts on ecosystem services of land use transitions to second‐generation bioenergy crops in GB

We present the first assessment of the impact of land use change (LUC) to second‐generation (2G) bioenergy crops on ecosystem services (ES) resolved spatially for Great Britain (GB). A systematic approach was used to assess available evidence on the impacts of LUC from arable, semi‐improved grassland or woodland/forest, to 2G bioenergy crops, for which a quantitative ‘threat matrix’ was developed. The threat matrix was used to estimate potential impacts of transitions to either Miscanthus, short‐rotation coppice (SRC, willow and poplar) or short‐rotation forestry (SRF). The ES effects were found to be largely dependent on previous land uses rather than the choice of 2G crop when assessing the technical potential of available biomass with a transition from arable crops resulting in the most positive effect on ES. Combining these data with constraint masks and available land for SRC and Miscanthus (SRF omitted from this stage due to lack of data), south‐west and north‐west England were identified as areas where Miscanthus and SRC could be grown, respectively, with favourable combinations of economic viability, carbon sequestration, high yield and positive ES benefits. This study also suggests that not all prospective planting of Miscanthus and SRC can be allocated to agricultural land class (ALC) ALC 3 and ALC 4 and suitable areas of ALC 5 are only minimally available. Beneficial impacts were found on 146 583 and 71 890 ha when planting Miscanthus or SRC, respectively, under baseline planting conditions rising to 293 247 and 91 318 ha, respectively, under 2020 planting scenarios. The results provide an insight into the interplay between land availability, original land uses, bioenergy crop type and yield in determining overall positive or negative impacts of bioenergy cropping on ecosystems services and go some way towards developing a framework for quantifying wider ES impacts of this important LUC.     

Targeted Next Generation Sequencing as a Reliable Diagnostic Assay for the Detection of Somatic Mutations in Tumours Using Minimal DNA Amounts from Formalin Fixed Paraffin Embedded Material

Background

Targeted Next Generation Sequencing (NGS) offers a way to implement testing of multiple genetic aberrations in diagnostic pathology practice, which is necessary for personalized cancer treatment. However, no standards regarding input material have been defined. This study therefore aimed to determine the effect of the type of input material (e.g. formalin fixed paraffin embedded (FFPE) versus fresh frozen (FF) tissue) on NGS derived results. Moreover, this study aimed to explore a standardized analysis pipeline to support consistent clinical decision-making.

Method

We used the Ion Torrent PGM sequencing platform in combination with the Ion AmpliSeq Cancer Hotspot Panel v2 to sequence frequently mutated regions in 50 cancer related genes, and validated the NGS detected variants in 250 FFPE samples using standard diagnostic assays. Next, 386 tumour samples were sequenced to explore the effect of input material on variant detection variables. For variant calling, Ion Torrent analysis software was supplemented with additional variant annotation and filtering.

Results

Both FFPE and FF tissue could be sequenced reliably with a sensitivity of 99.1%. Validation showed a 98.5% concordance between NGS and conventional sequencing techniques, where NGS provided both the advantage of low input DNA concentration and the detection of low-frequency variants. The reliability of mutation analysis could be further improved with manual inspection of sequence data.

Conclusion

Targeted NGS can be reliably implemented in cancer diagnostics using both FFPE and FF tissue when using appropriate analysis settings, even with low input DNA.     

LncRNA GAS6‐AS2 promotes bladder cancer proliferation and metastasis via GAS6‐AS2/miR‐298/CDK9 axis

Long noncoding RNAs (lncRNAs) have been proved to play important roles in carcinogenesis and development of numerous cancers, but their biological functions in bladder cancer remain largely unknown. In this study, a novel lncRNA termed GAS6‐AS2 were primary identified, and its roles as well as mechanisms in regulating proliferation and metastasis of bladder cancer cells were investigated. Clinically, GAS6‐AS2 was significantly up‐regulated in bladder cancer tissues and positively correlated with tumour stages and poor prognosis. Moreover, expression of GAS6‐AS2 was also increased in bladder cancer cells compared with normal bladder cells. Further investigating the roles of GAS6‐AS2, we found GAS6‐AS2 regulated proliferation and proliferative activity of bladder cancer cells via inducing G1 phase arrest. What's more, we found that GAS6‐AS2 contributed to metastatic abilities of cells. In mechanism, GAS6‐AS2 could function as a competitive endogenous RNA (ceRNA) via direct sponging miR‐298, which further regulating the expression of CDK9. Finally, we also proved that GAS6‐AS2 knockdown suppressed tumour growth and metastasis in vivo. In conclusion, our study proved that GAS6‐AS2 could function as a ceRNA and promote the proliferation and metastasis of bladder cancer cells, which provided a novel prognostic marker for bladder cancer patients in clinic.     

Up‐regulation of ZFAS1 indicates dismal prognosis for cholangiocarcinoma and promotes proliferation and metastasis by modulating USF1 via miR‐296‐5p

LncRNAs has been demonstrated to modulate neoplastic development by modulating downstream miRNAs and functional genes. In this study, we aimed to detect the interaction among lncRNA ZFAS1 miR‐296‐5p and USF1. We explored the proliferation, migration and invasion of cholangiocarcinoma. The differentially expressed ZFAS1 was discovered in both tissues and cell lines by qRT‐PCR. The targeting relationship between miR‐296‐5p and ZFAS1 or USF1 was validated by dual‐luciferase assay. The impact of ZFAS1 on CCA cell proliferation was observed by CCK‐8 assay. The protein expression of USF1 was determined by Western blot. The effects of ZFAS1, miR‐296‐5p and USF1 on tumour growth were further confirmed using xenograft model. LncRNA ZFAS1 expression was relatively up‐regulated in tumour tissues and cells while miR‐296‐5p was significantly down‐regulated. Knockdown of ZFAS1 significantly suppressed tumour proliferation, migration, invasion and USF1 expression. Overexpressed miR‐296‐5p suppressed cell proliferation and metastasis. Knockdown of USF1 inhibited cell proliferation and metastasis and xenograft tumour growth. In conclusion, ZFAS1 might promote cholangiocarcinoma proliferation and metastasis by modulating USF1 via miR‐296‐5p.