北京地区两种虫媒病毒的监测

1984年我们对北京地区的乙型脑炎病毒和M14病毒进行了监测,观察到三带喙库蚊季节消长高峰在8月中旬,较发病率较高的1980年和1981年晚3周左右:乙型脑炎病毒检出率(批)为16.1％,最低现场感染率为1:303,检出高峰在8月中旬(44.0％),较1981年晚2周以上;到8月初才发现所感染的猪,明显晚于1980年和1981年,受上述众因素的影响,本年度本市乙型脑炎发病率仍较低(0.8/10万),在M14病毒的监测中,发现三带喙库蚊环病毒M14病毒检出率为9.32％,最低现场感染率为1:526,当年最高检出率(32％)和最低现场感染率高峰(1:156),高峰出现在8月30日,与乙脑病毒自然感染率出现的高蜂相一致;猪感染M14病毒与感染乙脑病毒的时间基本相同,表明这两种病毒在自然界传播中不存在明显的互相干扰关系,乙脑低流行年的出现并未受到M14病毒的影响。     

Whole exome sequencing of a Saudi family and systems biology analysis identifies CPED1 as a putative causative gene to Celiac Disease

Celiac disease (CD) is a gastrointestinal disorder whose genetic basis is not fully understood. Therefore, we studied a Saudi family with two CD affected siblings to discover the causal genetic defect. Through whole exome sequencing (WES), we identified that both siblings have inherited an extremely rare and deleterious CPED1 genetic variant (c.241 A > G; p.Thr81Ala) segregating as autosomal recessive mutation, suggesting its putative causal role in the CD. Saudi population specific minor allele frequency (MAF) analysis has confirmed its extremely rare prevalence in homozygous condition (MAF is 0.0004). The Sanger sequencing analysis confirmed the absence of this homozygous variant in 100 sporadic Saudi CD cases. Genotype-Tissue Expression (GTEx) data has revealed that CPED1 is abundantly expressed in gastrointestinal mucosa. By using a combination of systems biology approaches like protein 3D modeling, stability analysis and nucleotide sequence conservation analysis, we have further established that this variant is deleterious to the structural and functional aspects of CPED1 protein. To the best of our knowledge, this variant has not been previously reported in CD or any other gastrointestinal disease. The cell culture and animal model studies could provide further insight into the exact role of CPED1 p.Thr81Ala variant in the pathophysiology of CD. In conclusion, by using WES and systems biology analysis, present study for the first-time reports CPED1 as a potential causative gene for CD in a Saudi family with potential implications to both disease diagnosis and genetic counseling.     

Each meal matters in the exposome: Biological and community considerations in fast-food-socioeconomic associations

Advances in omics and microbiome technology have transformed the ways in which the biological consequences of life in the ‘ecological theatre' can be visualized. Exposome science examines the total accumulated environmental exposures (both detrimental and beneficial) as a means to understand the response of the ‘total organism to the total environment' over time. The repetitive stimulation of compensatory physiological responses (immune, cardiovascular, neuroendocrine) in response to stress – including sources of stress highly relevant to socioeconomic disadvantage – may lead to metabolic dysregulation and cellular damage, ultimately influencing behavior and disease. The collective toll of physiological wear and tear, known as allostatic load, is not paid equally throughout developed societies. It is paid in excess by the disadvantaged. In the context of fast-food, human and experimental research demonstrates that the biological response to a single fast-food-style meal – especially as mediated by the microbiome- is a product of the person's total lived experience, including the ability to buffer the fast-food meal-induced promotion of inflammation and oxidative stress. Emerging research indicates that each meal and its nutritional context matters. As we discuss, equal weekly visits to major fast-food outlets by the affluent and deprived do not translate into biological equivalency. Hence, debate concerning reducing fast-food outlets through policy – especially in disadvantaged neighborhoods where they are prevalent – requires a biological context. The fast-food establishment and fast-food meal – as they represent matters of food justice and press upon non-communicable disease risk – are far more than physical structures and collections of carbohydrate, fat, sugar and sodium.     

Spatial clustering of average risks and risk trends in Bayesian disease mapping

Spatiotemporal disease mapping focuses on estimating the spatial pattern in disease risk across a set of nonoverlapping areal units over a fixed period of time. The key aim of such research is to identify areas that have a high average level of disease risk or where disease risk is increasing over time, thus allowing public health interventions to be focused on these areas. Such aims are well suited to the statistical approach of clustering, and while much research has been done in this area in a purely spatial setting, only a handful of approaches have focused on spatiotemporal clustering of disease risk. Therefore, this paper outlines a new modeling approach for clustering spatiotemporal disease risk data, by clustering areas based on both their mean risk levels and the behavior of their temporal trends. The efficacy of the methodology is established by a simulation study, and is illustrated by a study of respiratory disease risk in Glasgow, Scotland.     

RNA binding protein RALY promotes Protein Arginine Methyltransferase 1 alternatively spliced isoform v2 relative expression and metastatic potential in breast cancer cells

Aberrant expression of Protein Arginine Methyltransferases (PRMTs) has been observed in several cancer types, including breast cancer. We previously reported that the PRMT1v2 isoform, which is generated through inclusion of alternative exon 2, is overexpressed in breast cancer cells and promotes their invasiveness. However, the precise mechanism by which expression of this isoform is controlled and how it is dysregulated in breast cancer remains unknown. Using a custom RNA interference-based screen, we identified several RNA binding proteins (RBP) which, when knocked down, altered the relative abundance of the alternatively spliced PRMT1v2 isoform. Amongst the top hits were SNW Domain containing 1 (SNW1) and RBP-associated with lethal yellow mutation (RALY), which both associated with the PRMT1 pre-mRNA and upon depletion caused an increase or decrease in the relative abundance of PRMT1v2 isoform mRNA and protein. Most importantly, a significant decrease in invasion was observed upon RALY knockdown in aggressive breast cancer cells, consistent with targeting PRMT1v2 directly, and this effect was rescued by the exogenous re-expression of PRMT1v2. We show that SNW1 expression is decreased, while RALY expression is increased in breast cancer cells and tumours, which correlates with decreased patient survival. This work revealed crucial insight into the mechanisms regulating the expression of the PRMT1 alternatively spliced isoform v2 and its dysregulation in breast cancer. It also provides proof-of-concept support for the development of therapeutic strategies where regulators of PRMT1 exon 2 alternative splicing are targeted as an approach to selectively reduce PRMT1v2 levels and metastasis in breast cancer.     

Peptides for optical medical imaging and steps towards therapy

Optical medical imaging is a rapidly growing area of research and development that offers a multitude of healthcare solutions both diagnostically and therapeutically. In this review, some of the most recently described peptide-based optical probes are reviewed with a special emphasis on their in vivo use and potential application in a clinical setting.