Redefining the common insertion site

AbstractRetroviral mutagenesis has been used as a powerful tool to discover genes involved in oncogenesis through a technique called Common Insertion Site (CIS) analysis where tumors are induced by proviral integrations and the genomic loci of the proviruses are identified. A fundamental assumption made in this analysis is that multiple proviral insertions in close proximity occurring more frequently than would be predicted randomly provides evidence that the genes near the integrations are involved in the formation of the tumors. We demonstrate here using data derived from MLV integrations not put under selection for tumor induction that CIS analysis as currently defined is often not a sufficient argument for a gene's significance in tumorigenesis

Integrated Laboratory Demonstrations of Multi-Object Adaptive Optics on a Simulated 10-Meter Telescope at Visible Wavelengths

One important frontier for astronomical adaptive optics (AO) involves methods such as Multi-Object AO and Multi-Conjugate AO that have the potential to give a significantly larger field of view than conventional AO techniques. A second key emphasis over the next decade will be to push astronomical AO to visible wavelengths. We have conducted the first laboratory simulations of wide-field, laser guide star adaptive optics at visible wavelengths on a 10-meter-class telescope. These experiments, utilizing the UCO/Lick Observatory's Multi-Object / Laser Tomography Adaptive Optics (MOAO/LTAO) testbed, demonstrate new techniques in wavefront sensing and control that are crucial to future on-sky MOAO systems. We (1) test and confirm the feasibility of highly accurate atmospheric tomography with laser guide stars, (2) demonstrate key innovations allowing open-loop operation of Shack-Hartmann wavefront sensors (with errors of ~30 nm) as will be needed for MOAO, and (3) build a complete error budget model describing system performance. The AO system maintains a performance of 32.4% Strehl on-axis, with 24.5% and 22.6% at 10" and 15", respectively, at a science wavelength of 710 nm (R-band) over the equivalent of 0.8 seconds of simulation. The MOAO-corrected field of view is ~25 times larger in area than that limited by anisoplanatism at R-band. Our error budget is composed of terms verified through independent, empirical experiments. Error terms arising from calibration inaccuracies and optical drift are comparable in magnitude to traditional terms like fitting error and tomographic error. This makes a strong case for implementing additional calibration facilities in future AO systems, including accelerometers on powered optics, 3D turbulators, telescope and LGS simulators, and external calibration ports for deformable mirrors.Comment: 29 pages, 11 figures, submitted to PAS

Polymorphism Interaction Analysis (PIA): a method for investigating complex gene-gene interactions

<p>Abstract</p> <p>Background</p> <p>The risk of common diseases is likely determined by the complex interplay between environmental and genetic factors, including single nucleotide polymorphisms (SNPs). Traditional methods of data analysis are poorly suited for detecting complex interactions due to sparseness of data in high dimensions, which often occurs when data are available for a large number of SNPs for a relatively small number of samples. Validation of associations observed using multiple methods should be implemented to minimize likelihood of false-positive associations. Moreover, high-throughput genotyping methods allow investigators to genotype thousands of SNPs at one time. Investigating associations for each individual SNP or interactions between SNPs using traditional approaches is inefficient and prone to false positives.</p> <p>Results</p> <p>We developed the Polymorphism Interaction Analysis tool (PIA version 2.0) to include different approaches for ranking and scoring SNP combinations, to account for imbalances between case and control ratios, stratify on particular factors, and examine associations of user-defined pathways (based on SNP or gene) with case status. PIA v. 2.0 detected 2-SNP interactions as the highest ranking model 77% of the time, using simulated data sets of genetic models of interaction (minor allele frequency = 0.2; heritability = 0.01; N = 1600) generated previously [Velez DR, White BC, Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH: A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol 2007, 31:306–315.]. Interacting SNPs were detected in both balanced (20 SNPs) and imbalanced data (case:control 1:2 and 1:4, 10 SNPs) in the context of non-interacting SNPs.</p> <p>Conclusion</p> <p>PIA v. 2.0 is a useful tool for exploring gene*gene or gene*environment interactions and identifying a small number of putative associations which may be investigated further using other statistical methods and in replication study populations.</p

Panama Bridge Project

The Panama Bridge project has partnered with Rio Missions Panama to design a bridge for the village of La Gigi, Panama. The mountain community of La Gigi experiences heavy rainfall during the rainy seasons. A stream runs along the community, restricting their access to schools, employment options, and other communities. While passable during dry seasons, the stream floods and becomes impassable after heavy rains. The residents are effectively cut off from their livelihoods, church, health services, and other communities during this time. To accommodate this need, the Panama Bridge Team has spent the last two academic years designing a 90 foot aluminum truss bridge. The design includes a unique construction strategy to deal with challenging site constraints.https://mosaic.messiah.edu/engr2021/1011/thumbnail.jp

Decreased microbial co-occurrence network stability and SCFA receptor level correlates with obesity in African-origin women.

We compared the gut microbial populations in 100 women, from rural Ghana and urban US [50% lean (BMI &lt; 25 kg/m2) and 50% obese (BMI ≥ 30 kg/m2)] to examine the ecological co-occurrence network topology of the gut microbiota as well as the relationship of short chain fatty acids (SCFAs) with obesity. Ghanaians consumed significantly more dietary fiber, had greater microbial alpha-diversity, different beta-diversity, and had a greater concentration of total fecal SCFAs (p-value &lt; 0.002). Lean Ghanaians had significantly greater network density, connectivity and stability than either obese Ghanaians, or lean and obese US participants (false discovery rate (FDR) corrected p-value ≤ 0.01). Bacteroides uniformis was significantly more abundant in lean women, irrespective of country (FDR corrected p &lt; 0.001), while lean Ghanaians had a significantly greater proportion of Ruminococcus callidus, Prevotella copri, and Escherichia coli, and smaller proportions of Lachnospiraceae, Bacteroides and Parabacteroides. Lean Ghanaians had a significantly greater abundance of predicted microbial genes that catalyzed the production of butyric acid via the fermentation of pyruvate or branched amino-acids, while obese Ghanaians and US women (irrespective of BMI) had a significantly greater abundance of predicted microbial genes that encoded for enzymes associated with the fermentation of amino-acids such as alanine, aspartate, lysine and glutamate. Similar to lean Ghanaian women, mice humanized with stool from the lean Ghanaian participant had a significantly lower abundance of family Lachnospiraceae and genus Bacteroides and Parabacteroides, and were resistant to obesity following 6-weeks of high fat feeding (p-value &lt; 0.01). Obesity-resistant mice also showed increased intestinal transcriptional expression of the free fatty acid (Ffa) receptor Ffa2, in spite of similar fecal SCFAs concentrations. We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of robust gut ecologic network in obesity

Associations between fears related to safety during sleep and self-reported sleep in men and women living in a low-socioeconomic status setting

South Africans living in low socioeconomic areas have self-reported unusually long sleep durations (approximately 9–10 h). One hypothesis is that these long durations may be a compensatory response to poor sleep quality as a result of stressful environments. This study aimed to investigate whether fear of not being safe during sleep is associated with markers of sleep quality or duration in men and women. South Africans (n = 411, 25–50 y, 57% women) of African-origin living in an urban township, characterised by high crime and poverty rates, participated in this study. Participants are part of a larger longitudinal cohort study: Modelling the Epidemiologic Transition Study (METS)–Microbiome. Customised questions were used to assess the presence or absence of fears related to feeling safe during sleep, and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index were used to assess daytime sleepiness, sleep quality and insomnia symptom severity respectively. Adjusted logistic regression models indicated that participants who reported fears related to safety during sleep were more likely to report poor sleep quality (PSQI &gt; 5) compared to participants not reporting such fears and that this relationship was stronger among men than women. This is one of the first studies outside American or European populations to suggest that poor quality sleep is associated with fear of personal safety in low-SES South African adults

Co-dependence between trypanosome nuclear lamina components in nuclear stability and control of gene expression

The nuclear lamina is a filamentous structure subtending the nuclear envelope and required for chromatin organization, transcriptional regulation and maintaining nuclear structure. The trypanosomatid coiled-coil NUP-1 protein is a lamina component functionally analogous to lamins, the major lamina proteins of metazoa. There is little evidence for shared ancestry, suggesting the presence of a distinct lamina system in trypanosomes. To find additional trypanosomatid lamina components we identified NUP-1 interacting proteins by affinity capture and mass-spectrometry. Multiple components of the nuclear pore complex (NPC) and a second coiled-coil protein, which we termed NUP-2, were found. NUP-2 has a punctate distribution at the nuclear periphery throughout the cell cycle and is in close proximity to NUP-1, the NPCs and telomeric chromosomal regions. RNAi-mediated silencing of NUP-2 leads to severe proliferation defects, gross alterations to nuclear structure, chromosomal organization and nuclear envelope architecture. Further, transcription is altered at telomere-proximal variant surface glycoprotein (VSG) expression sites (ESs), suggesting a role in controlling ES expression, although NUP-2 silencing does not increase VSG switching. Transcriptome analysis suggests specific alterations to Pol I-dependent transcription. NUP-1 is mislocalized in NUP-2 knockdown cells and vice versa, implying that NUP-1 and NUP-2 form a co-dependent network and identifying NUP-2 as a second trypanosomatid nuclear lamina component