HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma

Indexación: Web of ScienceBackground: Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown. Methods: Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2 alpha knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student's T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival. Results: Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2 alpha is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ER alpha) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated alpha-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset. Conclusions: Taking together, these results suggest that HDAC1 and HDAC6 may play a role in ccRCC biology and could represent rational therapeutic targets.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2604-

LincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint

The p53-regulated long noncoding RNA lincRNA-p21 has been proposed to act in trans via several mechanisms ranging from repressing genes in the p53 transcriptional network to regulating mRNA translation and protein stability. To further examine lincRNA-p21 function, we generated a conditional knockout mouse model. We find that lincRNA-p21 predominantly functions in cis to activate expression of its neighboring gene, p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a coactivator for p53-dependent p21 transcription. Additional phenotypes of lincRNA-p21 deficiency could be attributed to diminished p21 levels, including deregulated expression and altered chromatin state of some Polycomb target genes, a defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency. These findings indicate that lincRNA-p21 affects global gene expression and influences the p53 tumor suppressor pathway by acting in cis as a locus-restricted coactivator for p53-mediated p21 expression.National Institutes of Health (U.S.)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyDamon Runyon Cancer Research Foundatio

Carbon Monitoring System Flux Estimation and Attribution: Impact of ACOS-GOSAT X(CO2) Sampling on the Inference of Terrestrial Biospheric Sources and Sinks

Using an Observing System Simulation Experiment (OSSE), we investigate the impact of JAXA Greenhouse gases Observing SATellite 'IBUKI' (GOSAT) sampling on the estimation of terrestrial biospheric flux with the NASA Carbon Monitoring System Flux (CMS-Flux) estimation and attribution strategy. The simulated observations in the OSSE use the actual column carbon dioxide (X(CO2)) b2.9 retrieval sensitivity and quality control for the year 2010 processed through the Atmospheric CO2 Observations from Space algorithm. CMS-Flux is a variational inversion system that uses the GEOS-Chem forward and adjoint model forced by a suite of observationally constrained fluxes from ocean, land and anthropogenic models. We investigate the impact of GOSAT sampling on flux estimation in two aspects: 1) random error uncertainty reduction and 2) the global and regional bias in posterior flux resulted from the spatiotemporally biased GOSAT sampling. Based on Monte Carlo calculations, we find that global average flux uncertainty reduction ranges from 25% in September to 60% in July. When aggregated to the 11 land regions designated by the phase 3 of the Atmospheric Tracer Transport Model Intercomparison Project, the annual mean uncertainty reduction ranges from 10% over North American boreal to 38% over South American temperate, which is driven by observational coverage and the magnitude of prior flux uncertainty. The uncertainty reduction over the South American tropical region is 30%, even with sparse observation coverage. We show that this reduction results from the large prior flux uncertainty and the impact of non-local observations. Given the assumed prior error statistics, the degree of freedom for signal is approx.1132 for 1-yr of the 74 055 GOSAT X(CO2) observations, which indicates that GOSAT provides approx.1132 independent pieces of information about surface fluxes. We quantify the impact of GOSAT's spatiotemporally sampling on the posterior flux, and find that a 0.7 gigatons of carbon bias in the global annual posterior flux resulted from the seasonally and diurnally biased sampling when using a diagonal prior flux error covariance

Tree sequences as a general-purpose tool for population genetic inference

As population genetics data increases in size new methods have been developed to store genetic information in efficient ways, such as tree sequences. These data structures are computationally and storage efficient, but are not interchangeable with existing data structures used for many population genetic inference methodologies such as the use of convolutional neural networks (CNNs) applied to population genetic alignments. To better utilize these new data structures we propose and implement a graph convolutional network (GCN) to directly learn from tree sequence topology and node data, allowing for the use of neural network applications without an intermediate step of converting tree sequences to population genetic alignment format. We then compare our approach to standard CNN approaches on a set of previously defined benchmarking tasks including recombination rate estimation, positive selection detection, introgression detection, and demographic model parameter inference. We show that tree sequences can be directly learned from using a GCN approach and can be used to perform well on these common population genetics inference tasks with accuracies roughly matching or even exceeding that of a CNN-based method. As tree sequences become more widely used in population genetics research we foresee developments and optimizations of this work to provide a foundation for population genetics inference moving forward

Remember Where You Came From

117 pagesThe goal of this book is to demystify historic preservation for communities interested in potentially designating their own historic industrial sites. It will also benefit those interested in industrial history, and historic preservation professionals. The companion booklet does a deep dive into historic preservation terminology, framework, and funding options for reference. Topics include the use of historic preservation terminology, the invention of United States heritage and the historical perceptions of the working class, historic significance and industrial landscapes, the history of graffiti and how it ties into industrial preservation, and an economic resources guide. This user-friendly format allows readers to refer to the history, theory, and definitions; focus on the policies and solutions; or utilize any combination the reader finds most useful. The examples demonstrated are meant to showcase tangible strategies and the problem-solving methods used by different institutions, with a focus on how they personally decided to develop and interpret their own industrial heritage with public use of the site in mind. Often, comprehending the designation of historic sites can be limited by academic and institutional rules, regulations, and shop talk. Despite the process of nominating historic sites being open to the public, knowledge regarding the information and resources contained in this book is too often unknown, creating an unbalanced representation of the diversity of communities. Therefore, the systems of historic interpretation, historic preservation legal framework, and development will be explored in the companion book. Transparency and education about methods are important for each communities’ ability to use the information provided in this book to decentralize knowledge from the hands of “experts” and to provide an intro to the knowledge and tools for people to share their own histories and make their own community decisions. I hope that further representation of industrial communities’ histories empowers those communities and aids in sharing their complete history. Challenges come with compressing an incredibly complex topic and that will result in gaps of information. There are so many more sites, towns, and people impacted by the industrial past. There is always room for improvement and hopefully this will just be the first edition of this title, augmented by future communities, authors, contributors, resources, research, and interpretations

Implementing Eco-Friendly Housing Techniques in Western Montana: Green Home Montana: Eco-friendly Housing and Living Practices - Final Capstone Portfolio

While the green building movement is common practice in the commercial realm, it is not yet widely popular with residential buildings. We considered the question “How can residents of western Montana adopt eco-friendly housing practices that are locally appropriate and relevant?” There is an opportunity to increase green living practices among renters and homeowners in western Montana through retrofitting, gardening, composting, and similar behaviors. By considering climatic factors relevant to the region, suggestions for relevant eco-friendly practices can be made available to homeowners and renters alike. We will research green living practices used in other countries with similar climatic factors as western Montana. We will then make a website to help streamline locally relevant information catered to help residents take action towards their sustainability goals. We will survey a sample of residents throughout western Montana to inform the materials provided on the website. For example, these materials may include, but are not limited to, sustainability project demonstration videos, links to local builders, history, blogs, global initiatives, and links to other resources. We expect this website to be relevant and increase accessibility to western Montana renters and homeowners

UC-39 Journalistic Integrity vis Artifical Intelligence

We are developing a web app to recognize and rate political bias in online journalism using artificial intelligence. All human writing inherently contains bias ,however bias is less harmful if it is transparent to the reader because they can now make informed decisions about what they read. We\u27ve collected articles and and reactions to them from online sources, and then used Neural Networks trained for natural language processing to determine bias. The project can predict bias labels on a news articles with 82% accuracy.Advisors(s): Reza Meimandi Parizi - course instructor Asher Nuckolls - project ownerTopic(s): Artificial IntelligenceSWE472

Early life stress is associated with greater negative emotionality and peripheral inflammation in alcohol use disorder.

Early life stress (ELS) increases risk for psychiatric illness, including alcohol use disorder (AUD). Researchers have hypothesized that individuals with and without a history of ELS who have the same primary DSM-5 diagnosis are clinically and biologically distinct. While there is strong support for this hypothesis in the context of mood disorders, the hypothesis remains largely untested in the context of AUD. This study investigated the impact of ELS on the neuroclinical phenomenology and inflammatory profile of individuals with AUD. Treatment-seeking adults with AUD (N = 163) completed the Adverse Childhood Experiences (ACE) Questionnaire and phenotypic battery as part of a pharmacotherapy trial for AUD (NCT03594435). Participants were classified as having no-ELS, (ACE = 0) moderate-ELS, (ACE = 1, 2 or 3) or high-ELS (ACE = 4 + ). The Addictions Neuroclinical Assessment domains incentive salience and negative emotionality were derived and used to assess the neuroclinical phenomenology of AUD. We tested (1) cumulative ELS as a predictor of ANA domains and (2) ELS group differences in ANA domains. A subset of participants (N = 98) provided blood samples for a biomarker of peripheral inflammation (C-reactive protein; CRP); analyses were repeated with CRP as the outcome variable. Greater ELS predicted higher negative emotionality and elevated CRP, but not incentive salience. The high-ELS group exhibited greater negative emotionality compared with the no-ELS and moderate-ELS groups, with no difference between the latter two groups. The high-ELS group exhibited elevated CRP compared with the no/moderate-ELS group. Findings suggest that high-ELS exposure is associated with a unique AUD neuroclinical presentation marked by greater negative emotionality, and inflammatory profile characterized by elevated peripheral CRP

OpenEarable:Open Hardware Earable Sensing Platform

Earables are ear-worn devices that offer functionalities beyond basic audio in- and output. In this paper we present the ongoing development of a new, open-source, Arduino-based earable platform called OpenEarable. It is based on standard components, is easy to manufacture and costs roughly $40 per device at batch size ten. We present the first version of the device which is equipped with a series of sensors and actuators: a 3-axis accelerometer and gyroscope, an ear canal pressure and temperature sensor, an inward facing ultrasonic microphone as well as a speaker, a push button, and a controllable LED. We demonstrate the versatility of the prototyping platform through three different example application scenarios. In sum, OpenEarable offers a general-purpose, open sensing platform for earable research and development.<br/

Three-dimensional trajectories and network analyses of group behaviour within chimney swift flocks during approaches to the roost

Chimney swifts (Chaetura pelagica) are highly manoeuvrable birds notable for roosting overnight in chimneys, in groups of hundreds or thousands of birds, before and during their autumn migration. At dusk, birds gather in large numbers from surrounding areas near a roost site. The whole flock then employs an orderly, but dynamic, circling approach pattern before rapidly entering a small aperture en masse. We recorded the three-dimensional trajectories of ≈1 800 individual birds during a 30 min period encompassing flock formation, circling, and landing, and used these trajectories to test several hypotheses relating to flock or group behaviour. Specifically, we investigated whether the swifts use local interaction rules based on topological distance (e.g. the n nearest neighbours, regardless of their distance) rather than physical distance (e.g. neighbours within x m, regardless of number) to guide interactions, whether the chimney entry zone is more or less cooperative than the surrounding flock, and whether the characteristic subgroup size is constant or varies with flock density. We found that the swift flock is structured around local rules based on physical distance, that subgroup size increases with density, and that there exist regions of the flock that are less cooperative than others, in particular the chimney entry zone