Allele-specific transcriptional elongation regulates monoallelic expression of the IGF2BP1 gene

<p>Abstract</p> <p>Background</p> <p>Random monoallelic expression contributes to phenotypic variation of cells and organisms. However, the epigenetic mechanisms by which individual alleles are randomly selected for expression are not known. Taking cues from chromatin signatures at imprinted gene loci such as the insulin-like growth factor 2 gene 2 (<it>IGF2</it>), we evaluated the contribution of CTCF, a zinc finger protein required for parent-of-origin-specific expression of the <it>IGF2 </it>gene, as well as a role for allele-specific association with DNA methylation, histone modification and RNA polymerase II.</p> <p>Results</p> <p>Using array-based chromatin immunoprecipitation, we identified 293 genomic loci that are associated with both CTCF and histone H3 trimethylated at lysine 9 (H3K9me3). A comparison of their genomic positions with those of previously published monoallelically expressed genes revealed no significant overlap between allele-specifically expressed genes and colocalized CTCF/H3K9me3. To analyze the contributions of CTCF and H3K9me3 to gene regulation in more detail, we focused on the monoallelically expressed <it>IGF2BP1 </it>gene. <it>In vitro </it>binding assays using the CTCF target motif at the <it>IGF2BP1 </it>gene, as well as allele-specific analysis of cytosine methylation and CTCF binding, revealed that CTCF does not regulate mono- or biallelic <it>IGF2BP1 </it>expression. Surprisingly, we found that RNA polymerase II is detected on both the maternal and paternal alleles in B lymphoblasts that express <it>IGF2BP1 </it>primarily from one allele. Thus, allele-specific control of RNA polymerase II elongation regulates the allelic bias of <it>IGF2BP1 </it>gene expression.</p> <p>Conclusions</p> <p>Colocalization of CTCF and H3K9me3 does not represent a reliable chromatin signature indicative of monoallelic expression. Moreover, association of individual alleles with both active (H3K4me3) and silent (H3K27me3) chromatin modifications (allelic bivalent chromatin) or with RNA polymerase II also fails to identify monoallelically expressed gene loci. The selection of individual alleles for expression occurs in part during transcription elongation.</p

Increasing Academic Success in Undergraduate Engineering Education using Learning Analytics: A Design-Based Research Project

This paper describes the first iteration of a design-based research project that developed an early warning system (EWS) for an undergraduate engineering mentoring program. Using near real-time data from a university’s learning management system, we provided academic mentors with timely and targeted data on students’ developing academic progress. Over two design phases, we developed an EWS and examined how mentors used the EWS in their support activities. Findings from this iteration of the project point to the importance of locating analytics-based interventions within and across multiple activity systems that link mentors’ interactions with an EWS and their interventions with students.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106032/1/aera2012_krumm_learning_analytics.pd

What Will You Do for the Rest of the Day?

Understanding and predicting human mobility is vital to a large number of applications, ranging from recommendations to safety and urban service planning. In some travel applications, the ability to accurately predict the user's future trajectory is vital for delivering high quality of service. The accurate prediction of detailed trajectories would empower location-based service providers with the ability to deliver more precise recommendations to users. Existing work on human mobility prediction has mainly focused on the prediction of the next location (or the set of locations) visited by the user, rather than on the prediction of the continuous trajectory (sequences of further locations and the corresponding arrival and departure times). Furthermore, existing approaches often return predicted locations as regions with coarse granularity rather than geographical coordinates, which limits the practicality of the prediction. In this paper, we introduce a novel trajectory prediction problem: given historical data and a user's initial trajectory in the morning, can we predict the user's full trajectory later in the day (e.g. the afternoon trajectory)? The predicted continuous trajectory includes the sequence of future locations, the stay times, and the departure times. We first conduct a comprehensive analysis about the relationship between morning trajectories and the corresponding afternoon trajectories, and found there is a positive correlation between them. Our proposed method combines similarity metrics over the extracted temporal sequences of locations to estimate similar informative segments across user trajectories. Our evaluation shows results on both labeled and geographical trajectories with a prediction error reduced by 10-35% in comparison to the baselines. This improvement has the potential to enable precise location services, raising usefulness to users to unprecedented levels. We also present empirical evaluations with Markov model and Long Short Term Memory (LSTM), a state-of-the-art Recurrent Neural Network model. Our proposed method is shown to be more effective when smaller number of samples are used and is exponentially more efficient than LSTM.</jats:p

Privacy Architectures: Reasoning About Data Minimisation and Integrity

Privacy by design will become a legal obligation in the European Community if the Data Protection Regulation eventually gets adopted. However, taking into account privacy requirements in the design of a system is a challenging task. We propose an approach based on the specification of privacy architectures and focus on a key aspect of privacy, data minimisation, and its tension with integrity requirements. We illustrate our formal framework through a smart metering case study.Comment: appears in STM - 10th International Workshop on Security and Trust Management 8743 (2014

Resistance management and integrated pest management insights from deployment of a Cry3Bb1+ Gpp34Ab1/Tpp35Ab1 pyramid in a resistant western corn rootworm landscape

In Nebraska USA, many populations of western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, now exhibit some level of resistance to all corn rootworm-active Bacillus thuringiensis Berliner (Bt) proteins expressed in commercial hybrids. Therefore, a study was conducted in northeast Nebraska from 2020–2022 to reevaluate current corn rootworm management options in continuous maize (consecutive planting for ≥2 years). Results from on-farm experiments to evaluate a standard soil-applied insecticide (Aztec® 4.67G) in combination with non-rootworm Bt or rootworm-active Bt pyramided maize (Cry3Bb1 + Gpp34Ab1/Tpp35Ab1) are reported within the context of WCR Bt resistance levels present. Corrected survival from Bt pyramid single-plant bioassays (\u3c0.3, 0.3–0.49, \u3e0.5) was used to place populations into 3 resistance categories. Variables evaluated included root injury, adult emergence, proportion lodged maize, and grain yield. Key results: A composite analysis of all populations across resistance levels indicated that addition of soil insecticide to Bt pyramid significantly reduced adult emergence and lodging but did not significantly increase root protection or yield. Within and among resistance category analyses of root injury revealed that the Bt pyramid remained highly efficacious at any non-rootworm Bt root injury level when resistance was absent or low. When corrected survival was \u3e0.3, mean Bt pyramid root injury tracked more closely in a positive linear fashion with mean non-rootworm Bt root injury (rootworm density x level of resistance interaction). Similar trends were obtained for adult emergence but not yield. Mean Bt pyramid root injury rating was \u3c0.75 in most populations with Bt resistance, which contributed to no significant yield differences among categories. Results are discussed within the context of IPM:IRM tradeoffs and the need to reduce WCR densities in this system to decrease the impact of the density x resistance interaction to bridge use of current pyramids with new technologies introduced over the next decade

21-cm synthesis observations of VIRGOHI 21 - a possible dark galaxy in the Virgo Cluster

Many observations indicate that dark matter dominates the extra-galactic Universe, yet no totally dark structure of galactic proportions has ever been convincingly identified. Previously we have suggested that VIRGOHI 21, a 21-cm source we found in the Virgo Cluster using Jodrell Bank, was a possible dark galaxy because of its broad line-width (~200 km/s) unaccompanied by any visible gravitational source to account for it. We have now imaged VIRGOHI 21 in the neutral-hydrogen line and find what could be a dark, edge-on, spinning disk with the mass and diameter of a typical spiral galaxy. Moreover, VIRGOHI 21 has unquestionably been involved in an interaction with NGC 4254, a luminous spiral with an odd one-armed morphology, but lacking the massive interactor normally linked with such a feature. Numerical models of NGC 4254 call for a close interaction ~10^8 years ago with a perturber of ~10^11 solar masses. This we take as additional evidence for the massive nature of VIRGOHI 21 as there does not appear to be any other viable candidate. We have also used the Hubble Space Telescope to search for stars associated with the HI and find none down to an I band surface brightness limit of 31.1 +/- 0.2 mag/sq. arcsec.Comment: 8 pages, accepted to ApJ, uses emulateapj.cls. Mpeg animation (Fig. 2) available at ftp://ftp.naic.edu/pub/publications/minchin/video2.mp

FACT -- the First Cherenkov Telescope using a G-APD Camera for TeV Gamma-ray Astronomy (HEAD 2010)

Geiger-mode Avalanche Photodiodes (G-APD) bear the potential to significantly improve the sensitivity of Imaging Air Cherenkov Telescopes (IACT). We are currently building the First G-APD Cherenkov Telescope (FACT) by refurbishing an old IACT with a mirror area of 9.5 square meters and construct a new, fine pixelized camera using novel G-APDs. The main goal is to evaluate the performance of a complete system by observing very high energy gamma-rays from the Crab Nebula. This is an important field test to check the feasibility of G-APD-based cameras to replace at some time the PMT-based cameras of planned future IACTs like AGIS and CTA. In this article, we present the basic design of such a camera as well as some important details to be taken into account.Comment: Poster shown at HEAD 2010, Big Island, Hawaii, March 1-4, 201

From Social Data Mining to Forecasting Socio-Economic Crisis

Socio-economic data mining has a great potential in terms of gaining a better understanding of problems that our economy and society are facing, such as financial instability, shortages of resources, or conflicts. Without large-scale data mining, progress in these areas seems hard or impossible. Therefore, a suitable, distributed data mining infrastructure and research centers should be built in Europe. It also appears appropriate to build a network of Crisis Observatories. They can be imagined as laboratories devoted to the gathering and processing of enormous volumes of data on both natural systems such as the Earth and its ecosystem, as well as on human techno-socio-economic systems, so as to gain early warnings of impending events. Reality mining provides the chance to adapt more quickly and more accurately to changing situations. Further opportunities arise by individually customized services, which however should be provided in a privacy-respecting way. This requires the development of novel ICT (such as a self- organizing Web), but most likely new legal regulations and suitable institutions as well. As long as such regulations are lacking on a world-wide scale, it is in the public interest that scientists explore what can be done with the huge data available. Big data do have the potential to change or even threaten democratic societies. The same applies to sudden and large-scale failures of ICT systems. Therefore, dealing with data must be done with a large degree of responsibility and care. Self-interests of individuals, companies or institutions have limits, where the public interest is affected, and public interest is not a sufficient justification to violate human rights of individuals. Privacy is a high good, as confidentiality is, and damaging it would have serious side effects for society.Comment: 65 pages, 1 figure, Visioneer White Paper, see http://www.visioneer.ethz.c

Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements

Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods. We applied 5C to analyze a 400-kb region containing the human beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by detection of several previously identified looping interactions in the beta-globin locus. We also identified a new looping interaction in K562 cells between the beta-globin Locus Control Region and the gamma-beta-globin intergenic region. Interestingly, this region has been implicated in the control of developmental globin gene switching. 5C should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure