以任何方法剪接:Mdm2位于肿瘤监视的十字路口

鼠双微基因2(Mdm2)是p53最重要的调节基因,同时也是对各种类型细胞应激(包DNA损害和致癌损伤)的主要应答者。尽管已有文章描述了Mdm2基因的替代产物的异常拼接产物,但是关于该变异体的起源、功能和影响,现在尚不清楚。最近发现了一种新的mdm2基因的剪接形式。在该剪接体中,108bp的基因内序列合并到成熟的Mdm2 mRNA中。编码框内终止密码子的额外序列可使Mdm2蛋白明显缩短。最有趣的现象是,阿霉素和放线菌素D能诱导产生一种交替剪接形式,即成熟的Mdm2+108,而其他的DNA损伤剂没有这种诱导作用。Mdm2+108基因可诱导p53的大量快速聚集,证明该交替剪接事件的作用是形成p53的肿瘤监视途径,同时抑制细胞的增殖(该细胞为被有效的遗传毒性化合物所破坏的细胞)。

Quantitative analysis of opioids and cannabinoids in wastewater samples

Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in defined population groups.We developed and validated an analytical method for the simultaneous determination of opioids(morphine,oxycodone,hydrocodone,oxymorphone and hydromorphone),and cannabinoids(△9-tetrahydrocannabinol,11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH)and THCCOOH-glucuronide)in raw-influent wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry.Method validation included linearity(5-1000 ng/L for opioids,10-1000 ng/L for cannabinoids),imprecision(<21.2%),accuracy(83%-131%),matrix effect(from-35.1%to-14.7%)and extraction efficiency(25%-84%),limit of detection(1-5 ng/L)and quantification(5-10 ng/L)and auto-sampler stability(no loss detected).River and wastewater samples were collected in triplicate from different locations in New York City and stored at-20℃until analysis.Water from sewage overflow location tested positive for morphine(10.7 ng/L),oxycodone(4.2-23.5 ng/L),oxymorphone(4.8 ng/L)and hydromorphone(4.2 ng/L).Raw influent wastewater samples tested positive for morphine(133.0-258.3 ng/L),oxycodone(31.1-63.6 ng/L),oxymorphone(16.0-56.8 ng/L),hydromorphone(6.8-18.0 ng/L),hydrocodone(4.0-12.8 ng/L)and THCCOOH(168.2-772.0 ng/L).This method is sensitive and specific for opioids and marijuana determination in wastewater samples.

Wastewater analysis for nicotine,cocaine,amphetamines,opioids and cannabis in New York City

According to current surveys and overdoses data,there is a drug crisis in the USA.Wastewater-based epidemiology(WBE)is an evolving discipline that analyses wastewater samples to detect drugs and metabolites to estimate drug consumption in a certain community.This study demonstrates how drug relative presence could be tracked by testing wastewater,providing real-time results,in different boroughs in New York City throughout 1 year.We developed and fully validated two analytical methods,one for 21 drugs and metabolites,including nicotine,cocaine,amphetamines,opioids and cannabis markers;and another for the normalization factor creatinine.Both methods were performed by liquid chromatography tandem mass spectrometry(LC-MS/MS)using positive electrospray ionization,achieving a limit of quantification of 5–10 ng/L for drugs and metabolites,and 0.01 mg/L for creatinine.These methods were applied to 48 one-time grab wastewater samples collected from six wastewater treatment plants in New York City(Manhattan,The Bronx,Queens and Brooklyn),eight different times throughout 2016,before and after major holidays,including Memorial Day,4th of July,Labour Day and New Year’s.In this study,the drug group normalized concentrations present in the wastewater samples,in decreasing order,were cocaine,nicotine,opioids,cannabis and amphetamines.When looking at individual compounds,the one with the highest normalized concentration was benzoylecgonine(BE),followed by cotinine,morphine and 11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH).To estimate community use,these concentrations were multiplied by the corresponding correction factor,and the most present were THCCOOH,followed by BE,cotinine and morphine.When comparing the treatment plants by drug group(nicotine,cocaine,amphetamines,opioids and cannabis),samples collected from The Bronx had the highest normalized concentrations for nicotine,cocaine and opioids;The Bronx and Manhattan for cannabis;and Manhattan and Queens for amphetamines.In most of the cases,no effect due to holiday was observed.This study provides the first snapshot of drug use in New York City and how that changes between key calendar dates employing wastewater analysis.

‘New’unintentionally produced PCBs in the Arctic

Contamination of the Arctic by legacy polychlorinated biphenyls(PCB)is well documented,but the more recent discovery of unintentionally produced(UP)PCBs in the Arctic is a cause for concern.Legacy PCBs are covered by existing international conventions and regular monitoring,and the UP congeners are covered by the Stockholm Convention and the U.S.Toxic Substances Control Act,but systematic monitoring and regulatory enforcement of UP-PCBs are lacking.Sources of UP-PCB are by-products of manufacturing(e.g.pigments)and from thermal sources(e.g.incinerators).Estimates of PCB emissions in China now show UP-PCB eclipsing emissions of legacy PCB.Here we discuss the 209 PCB-congener results from surface snow samples from Lomonosovfonna in 2010 and 2014,a glacial site on Svalbard which,in 2014,shows presence of PCB5,PCB11,and an unusually high amount of PCB52.While PCB5 and PCB11 may not be found in legacy PCB mixtures,PCB52 is in many PCB mixtures,yet dominates none of them as in the 2014 snow sample.Is it possible that these congeners are from UP-PCB processes?A search of the literature shows that PCB5,PCB11 and PCB52 are co-synthesis products of pigment production and that PCB5 and PCB11 are found in flue gas and ash from hazardous waste incineration.Of these,PCB11 has received greater attention in the literature.It has recently been consistently detected in the air,snow,soil and biota in the Arctic,evidence that PCB11 and possibly other UP-PCB congeners are global contaminants.Ice core measurements dating from 1957 to 2009 of PCBs in Svalbard reveal PCB11 presence throughout that period,indicating historic presence in the Arctic before being a focus of research elsewhere.Other UP-PCB need to be more fully investigated,especially from thermal sources.

Leveraging Learning to Improve Disaster Management Outcomes

Disaster management agencies should be exemplars of learning given the volatility of their operating environment. However, there are cognitive, social, and organizational barriers that prevent these organizations from learning. The purpose of this article is to use the Caribbean Disaster and Emergency Management Agency(CDEMA) as an example of an organization that achieves double-loop learning in spite of known barriers. This research shows significant learning variations in the CDEMA organization from the regional to the national level. The results demonstrate that the CDEMA Coordinating Unit and a few national member agencies achieve double-loop learning, while the opposite is true for many national disaster offices. Analysis of this variation is one contribution to the disaster management and organizational learning literature. The article also suggests that organizational culture is an important precursor to learning and adds a much needed case example to the management and learning literature. The study ends with a proposal for future research in the area of disaster management, culture and learning, and propositions for national disaster offices to consider in order to enhance double-loop learning.