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排序方式: 共有171条查询结果,搜索用时 15 毫秒
41.
Yingxiang Li Angela I. Park Haiwei Mou Cansu Colpan Aizhan Bizhanova Elliot Akama-Garren Nik Joshi Eric A. Hendrickson David Feldser Hao Yin Daniel G. Anderson Tyler Jacks Zhiping Weng Wen Xue 《Genome biology》2015,16(1)
Although chromosomal deletions and inversions are important in cancer, conventional methods for detecting DNA rearrangements require laborious indirect assays. Here we develop fluorescent reporters to rapidly quantify CRISPR/Cas9-mediated deletions and inversions. We find that inversion depends on the non-homologous end-joining enzyme LIG4. We also engineer deletions and inversions for a 50 kb Pten genomic region in mouse liver. We discover diverse yet sequence-specific indels at the rearrangement fusion sites. Moreover, we detect Cas9 cleavage at the fourth nucleotide on the non-complementary strand, leading to staggered instead of blunt DNA breaks. These reporters allow mechanisms of chromosomal rearrangements to be investigated.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0680-7) contains supplementary material, which is available to authorized users. 相似文献42.
43.
Transgenic Research - 相似文献
44.
Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin 总被引:5,自引:0,他引:5
Alaluf S Atkins D Barrett K Blount M Carter N Heath A 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2002,15(2):112-118
We have examined the quantity and composition of melanin in both photoprotected (volar upper arm) and chronically photoexposed (dorsal forearm) skin from a range of different ethnic skin types including African, Indian, Mexican, Chinese and European. The most lightly pigmented (European, Chinese and Mexican) skin types have approximately half as much epidermal melanin as the most darkly pigmented (African and Indian) skin types. However, the composition of melanin in these lighter skin types is comparatively more enriched with lightly coloured, alkali-soluble melanin components (up to three-fold). Regardless of ethnicity, epidermal melanin content is significantly greater in chronically photoexposed skin than it is in corresponding photoprotected skin (up to two-fold). However, by comparison there is only a modest enrichment of lightly coloured, alkali soluble melanin components in photoprotected skin (up to 1.3-fold). Analysis of melanosomes extracted from the epidermis in these subjects indicates that the proportion of spheroidal melanosomes is low in all skin types examined (<10%). This suggests that in human skin, pheomelanin is a very minor component of epidermal melanin, even in the lightest (European) skin types. Analysis of melanosome size revealed a significant and progressive variation in size with ethnicity: African skin having the largest melanosomes followed in turn by Indian, Mexican, Chinese and European. On the basis of these findings, we propose that variation in skin pigmentation is strongly influenced by both the amount and the composition (or colour) of the melanin in the epidermis. Variation in melanosome size may also play a significant role. However, the data also suggest that in human skin there are subtle differences in the mechanisms associated with the maintenance of constitutive pigmentation and facultative hyperpigmentation, respectively. 相似文献
45.
Anecdotal reports suggest that people may be affected more by media coverage of animal rather than human-related abuse. Findings of the extant research regarding this apparent effect are mixed and omit certain key variables that may drive differential reactions to abuse disclosure. The goal of the current study was therefore to examine whether differences exist between individuals' emotional responses and pro-social behavior (reporting abuse) with respect to human (infant), or animal (puppy), directed abuse, and the effect of demographic and personality variables (including empathy and attitude to animals) on these responses. One hundred and twenty-three university students (104 females, 19 males) were presented with two scenarios (randomly presented to control for order effects) describing identical abuse situations but with two different “victims”—namely an infant or a puppy. Immediately after reading each scenario they were asked to indicate how much what the infant/puppy went through “bothered” them, the likelihood of their contacting the police should they know or discover the identity of the attacker, and complete the Profile of Mood States (Short Form). Results indicated that although in general participants were more bothered by the infant-than the puppy-abuse scenario, this was mediated by whether participants were current pet owners, and their level of pet attachment. Specifically, those most attached to their pet were significantly more bothered by the puppy abuse scenario than any other group. Personality and demographic characteristics were also found to relate to mood disturbance, bother rating, and willingness to contact police following each scenario. 相似文献
46.
Nik J. Cunniffe Francisco F. Laranjeira Franco M. Neri R. Erik DeSimone Christopher A. Gilligan 《PLoS computational biology》2014,10(8)
A spatially-explicit, stochastic model is developed for Bahia bark scaling, a threat to citrus production in north-eastern Brazil, and is used to assess epidemiological principles underlying the cost-effectiveness of disease control strategies. The model is fitted via Markov chain Monte Carlo with data augmentation to snapshots of disease spread derived from a previously-reported multi-year experiment. Goodness-of-fit tests strongly supported the fit of the model, even though the detailed etiology of the disease is unknown and was not explicitly included in the model. Key epidemiological parameters including the infection rate, incubation period and scale of dispersal are estimated from the spread data. This allows us to scale-up the experimental results to predict the effect of the level of initial inoculum on disease progression in a typically-sized citrus grove. The efficacies of two cultural control measures are assessed: altering the spacing of host plants, and roguing symptomatic trees. Reducing planting density can slow disease spread significantly if the distance between hosts is sufficiently large. However, low density groves have fewer plants per hectare. The optimum density of productive plants is therefore recovered at an intermediate host spacing. Roguing, even when detection of symptomatic plants is imperfect, can lead to very effective control. However, scouting for disease symptoms incurs a cost. We use the model to balance the cost of scouting against the number of plants lost to disease, and show how to determine a roguing schedule that optimises profit. The trade-offs underlying the two optima we identify—the optimal host spacing and the optimal roguing schedule—are applicable to many pathosystems. Our work demonstrates how a carefully parameterised mathematical model can be used to find these optima. It also illustrates how mathematical models can be used in even this most challenging of situations in which the underlying epidemiology is ill-understood. 相似文献
47.
Umi Shakina Haridan Umairah Mokhtar Lee R. Machado Abu Thalhah Abdul Aziz Rafidah Hanim Shueb Masliza Zaid Benedict Sim Mahiran Mustafa Nik Khairudin Nik Yusof Christopher K. C. Lee Suhaili Abu Bakar Sazaly AbuBakar Edward J. Hollox Hoh Boon Peng 《PloS one》2015,10(1)
The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method’s performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs. 相似文献
48.
In this paper, we explore the tensions around a recent controversial development in medical tourism: xenotourism in Mexico. We take this bioendeavor – now ceased – to be emblematic of the global character of contemporary biomedicine, providing insights into the production and operation of scientific knowledge. We explore this through what we call the “textures of globalization”: the anxiety regarding the extent to which Mexico was understood as an (in)appropriate venue for the generation of novel knowledge on xenotransplantation, and as a location for xenotourism. These tensions, which oscillated between calls for individual freedom (choice) and global regulation (standardization), ultimately led to the closure of xenotourism in Mexico. 相似文献
49.
Alessandri AL Duffin R Leitch AE Lucas CD Sheldrake TA Dorward DA Hirani N Pinho V de Sousa LP Teixeira MM Lyons JF Haslett C Rossi AG 《PloS one》2011,6(9):e25683
Background
Eosinophils not only defend the body against parasitic infection but are also involved in pathological inflammatory allergic diseases such as asthma, allergic rhinitis and contact dermatitis. Clearance of apoptotic eosinophils by macrophages is a key process responsible for driving the resolution of eosinophilic inflammation and can be defective in allergic diseases. However, enhanced resolution of eosinophilic inflammation by deliberate induction of eosinophil apoptosis using pharmacological agents has not been previously demonstrated. Here we investigated the effect of a novel cyclin-dependent kinase inhibitor drug, AT7519, on human and mouse eosinophil apoptosis and examined whether it could enhance the resolution of a murine model of eosinophil-dominant inflammation in vivo.Methodology/Principal Findings
Eosinophils from blood of healthy donors were treated with AT7519 and apoptosis assessed morphologically and by flow-cytometric detection of annexin-V/propidium iodide staining. AT7519 induced eosinophil apoptosis in a concentration dependent manner. Therapeutic administration of AT7519 in eosinophil-dominant allergic inflammation was investigated using an established ovalbumin-sensitised mouse model of allergic pleurisy. Following ovalbumin challenge AT7519 was administered systemically at the peak of pleural inflammation and inflammatory cell infiltrate, apoptosis and evidence of macrophage phagocytosis of apoptotic eosinophils assessed at appropriate time points. Administration of AT7519 dramatically enhanced the resolution of allergic pleurisy via direct induction of eosinophil apoptosis without detriment to macrophage clearance of these cells. This enhanced resolution of inflammation was shown to be caspase-dependent as the effects of AT7519 were reduced by treatment with a broad spectrum caspase inhibitor (z-vad-fmk).Conclusions
Our data show that AT7519 induces human eosinophil apoptosis and enhances the resolution of a murine model of allergic pleurisy by inducing caspase-dependent eosinophil apoptosis and enhancing macrophage ingestion of apoptotic eosinophils. These findings demonstrate the utility of cyclin-dependent kinase inhibitors such as AT7519 as potential therapeutic agents for the treatment of eosinophil dominant allergic disorders. 相似文献50.
In this study, a novel continuous reactor has been developed to produce high quality methyl esters (biodiesel) from palm oil. A microporous TiO2/Al2O3 membrane was packed with potassium hydroxide catalyst supported on palm shell activated carbon. The central composite design (CCD) of response surface methodology (RSM) was employed to investigate the effects of reaction temperature, catalyst amount and cross flow circulation velocity on the production of biodiesel in the packed bed membrane reactor. The highest conversion of palm oil to biodiesel in the reactor was obtained at 70 °C employing 157.04 g catalyst per unit volume of the reactor and 0.21 cm/s cross flow circulation velocity. The physical and chemical properties of the produced biodiesel were determined and compared with the standard specifications. High quality palm oil biodiesel was produced by combination of heterogeneous alkali transesterification and separation processes in the packed bed membrane reactor. 相似文献