A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley

AIM： To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma （ESCC） among the Kashmiri population of Northern India. METHODS： All cases （n = 51） and controls （n = 150） were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases （n = 45） and inpatient controls （n = 150） with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient＇s age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls.RESULTS： Thirty-five of 45 （77.8%） histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed gerrnline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 （77.7%）, that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance （P 〈 0.05） with familial history of cancer （CD = 58）, suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable ＂Hakh＂ （CD = 19.5）, red chillies （CD = 20.2）, hot salty soda tea （CD = 2.37） and local baked bread （CD = 1.1）. CONCLUSION： Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and ＂Hakh＂, that are rich in nitrosoamines and familial cancer history.

Discovering broader antiviral strategies:Role of interferon-induced transmembrane proteins in virus infection

Host antiviral strategies have been studied for a long time,and the antibody response and T-cell response represent the classic host antiviral strategies.The entry of enveloped viruses into host cells is a complex process that could involve interactions ofmultiple viral glycoproteins and host-cell receptors.Blocking this process is the key to preventing infection.In general,antigenspecific neutralizing antibodies are thought to effectively bind to viral glycoproteins to block virus entry.However,there are other unknown host factors that inhibit or enhance the virus entry into the host cell.Recently,Yang et al.discovered that interferon-induced transmembrane protein-1(IFITM1)inhibited Epstein–Barr virus(EBV)infection in epithelial cells(ECs)by competing with viral glycoproteins to bind to Ephrin receptor A2(EphA2),thereby blocking this key entry receptor[1](Figure 1).Together with previous research,this finding hints at the importance of discovering broader host protective factors.ECs are known to be critical sites for EBV infection and replication.EphA2 has been reported as one of the most crucial EBV entry receptors on the EC surface,which binds to viral glycoprotein H/L(gH/gL)and glycoprotein B(gB)[2]to drive the internalization and fusion of EBV[3].However,ECs with low susceptibility to EBV can still express a high level of EphA2[4],raising questions about additional factors that influence host susceptibility.

Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage

Familial dysautonomia(FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1(ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD headed to the discovery that homozygous deletion of the mouse Elp1 gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different copy numbers of the human FD ELP1 transgene into the Elp1 knockout mouse(Elp1) and observed that human ELP1 expression rescues embryonic development in a dose-dependent manner. We then conducted a comprehensive transcriptome analysis in mouse embryos to identify genes and pathways whose expression correlates with the amount of ELP1. We found that ELP1 is essential for the expression of genes responsible for nervous system development. Further, gene length analysis of the differentially expressed genes showed that the loss of Elp1 mainly impacts the expression of long genes and that by gradually restoring Elongator, their expression is progressively rescued. Finally, through evaluation of co-expression modules, we identified gene sets with unique expression patterns that depended on ELP1 expression.

先导编辑的研究进展及应用前景

人类众多遗传性疾病是由于基因组突变所导致,而基于基因编辑技术的基因治疗策略,可从DNA层面对致病突变进行彻底修复,为疾病的治愈提供了新的可能.随着基因编辑技术的不断发展与突破,2019年新型DNA编辑工具先导编辑(PE)成功问世.PE技术并不会引起DNA双链断裂(DSBs),也无需单独引入DNA模板,即可实现基因编辑,可广泛应用于包括点突变及小片段的插入、删除等不同场景.与传统基因编辑工具相比,PE因其高编辑效率及低脱靶率,具备更高的有效性与安全性.本篇综述:(1)详细介绍了先导编辑的工作原理及发展历史.(2)概述了先导编辑系统的改良策略,包括相关酶的改造、工具RNA的结构改进以及递送方式的创新(3)梳理了辅助PE系统设计和分析的网页工具,简化了PE系统的搭建及使用流程.(4)系统总结了PE在疾病模型中的应用案例,并展望了未来的临床应用前景.

Nature:研究利用单细胞分析阐明癌症干细胞在脑癌中的关键角色

近日。来自麻省总医院、博德研究所及哈佛大学的研究人员通过联合研究，在单细胞水平上对脑瘤基因组进行了分析。他们发现。癌症干细胞或许能够诱发少突神经胶质瘤的发生，少突神经胶质瘤是一种缓慢发展但却非常难以治愈的脑癌，相关研究刊登于Nature杂志上。同时研究者还首次在人类脑瘤样本中鉴别出了癌症干细胞及其分化的后代细胞。

Nat Cell Biol:研究发现人肝细胞抵抗HCV感染的代谢过程

病毒感染是二十一世纪面临的主要医学挑战之一，从影响全球3％人口的丙肝病毒（HCV）流行病到最近爆发的西尼罗河病毒、寨卡病毒和埃博拉病毒感染。病毒缺乏进行自我复制所需的基础代谢机制。为了解决这个问题，它们劫持它们的宿主的代谢机制以便完成它们的生命周期和进行增殖。然而，科学家们仍然并没有很好地理解病毒与它们感染的有机体之间在代谢上的相互作用。这主要是因为人基因与代谢过程之间存在复杂的相互作用。