Coupling Transcriptional State to Large-Scale Repeat Expansions in Yeast

SummaryExpansions of simple DNA repeats cause numerous hereditary disorders in humans. Replication, repair, and transcription are implicated in the expansion process, but their relative contributions are yet to be distinguished. To separate the roles of replication and transcription in the expansion of Friedreich’s ataxia (GAA)n repeats, we designed two yeast genetic systems that utilize a galactose-inducible GAL1 promoter but contain these repeats in either the transcribed or nontranscribed region of a selectable cassette. We found that large-scale repeat expansions can occur in the lack of transcription. Induction of transcription strongly elevated the rate of expansions in both systems, indicating that active transcriptional state rather than transcription through the repeat per se affects this process. Furthermore, replication defects increased the rate of repeat expansions irrespective of transcriptional state. We present a model in which transcriptional state, linked to the nucleosomal density of a region, acts as a modulator of large-scale repeat expansions

Advanced Gastric Cancer in a Young Patient

Gastric cancer remains the second most common cancer in the world, and is usually found in men, especially those over 50 years of age. The diagnosis is made by endoscopic biopsy. The high frequency of late diagnosis or advanced stages accounts for the overall poor prognosis for this tumor. Surgery is the most frequently employed modality for both cure and palliation. However, most patients present with advanced disease that is incurable. We reported a rare case of young female patient aged 23 years old with advanced gastric carcinoma. The main clinical features were epigastric discomfort, vomiting, and weight loss. An abdominal mass was palpable on physical examination. Endoscopy showed a giant tumor mass causing gastric outlet obstruction, nodular lesion, ulcerative and hemorrhagic. The histopathologic examination revealed mucinous gastric carcinoma. Palliative resection could not be performed because the tumor tightly adhered to adjacent structures. Jejunostomy was performed to allow enteral nutrition. Best supportive care is very important to improve the quality of life

Submesoscale dispersion in the vicinity of the Deepwater Horizon spill

Reliable forecasts for the dispersion of oceanic contamination are important for coastal ecosystems, society and the economy as evidenced by the Deepwater Horizon oil spill in the Gulf of Mexico in 2010 and the Fukushima nuclear plant incident in the Pacific Ocean in 2011. Accurate prediction of pollutant pathways and concentrations at the ocean surface requires understanding ocean dynamics over a broad range of spatial scales. Fundamental questions concerning the structure of the velocity field at the submesoscales (100 meters to tens of kilometers, hours to days) remain unresolved due to a lack of synoptic measurements at these scales. \textcolor{black} {Using high-frequency position data provided by the near-simultaneous release of hundreds of accurately tracked surface drifters, we study the structure of submesoscale surface velocity fluctuations in the Northern Gulf Mexico. Observed two-point statistics confirm the accuracy of classic turbulence scaling laws at 200m$-$50km scales and clearly indicate that dispersion at the submesoscales is \textit{local}, driven predominantly by energetic submesoscale fluctuations.} The results demonstrate the feasibility and utility of deploying large clusters of drifting instruments to provide synoptic observations of spatial variability of the ocean surface velocity field. Our findings allow quantification of the submesoscale-driven dispersion missing in current operational circulation models and satellite altimeter-derived velocity fields.Comment: 9 pages, 6 figure

Inflation and Dark Energy from spectroscopy at z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at z < 1, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at 2 < z < 5, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

New family of inhomogeneous γ\gamma-law cosmologies: example of gravitational waves in a homogeneous p=ϱ/3p=\varrho/3 background

We present an explicit three-parameter class of $p=\gamma \varrho$, ($-1/3\leq\gamma<1$), cosmological models admitting a two-dimensional group $G_{2}$ of isometries acting on spacelike surfaces. The family is self-similar in the sense that it has a further homothetic vector field and it contains subfamilies of both (previously unknown) tilted and non-tilted Bianchi models with that equation of state. This is the first algebraically general class of solutions of this kind including dust inhomogeneous solutions. The whole class presents a universal spacelike big-bang singularity in the finite past. More interestingly, the case $p=\varrho /3$ constitutes a new two-parameter inhomogeneous subfamily which can be viewed as a Bianchi V background with a gravitational wave travelling orthogonally to the surfaces of transitivity of the $G_{2}$ group. This wave generates the {\it inhomogeneity} of the spacetime and is related to the sound waves {\it tilting} the perfect fluid. It seems to be the first explicit exact example of a gravitational wave travelling along a homogeneous background that has a realistic equation of state $p=\varrho /3$.Comment: LaTeX, 25 pages, 3 figures. Uses epsfig package. One reference added; minor changes. To appear in Phys.Rev.

New resources for functional analysis of omics data for the genus Aspergillus

<p>Abstract</p> <p>Background</p> <p>Detailed and comprehensive genome annotation can be considered a prerequisite for effective analysis and interpretation of omics data. As such, Gene Ontology (GO) annotation has become a well accepted framework for functional annotation. The genus <it>Aspergillus </it>comprises fungal species that are important model organisms, plant and human pathogens as well as industrial workhorses. However, GO annotation based on both computational predictions and extended manual curation has so far only been available for one of its species, namely <it>A. nidulans</it>.</p> <p>Results</p> <p>Based on protein homology, we mapped 97% of the 3,498 GO annotated <it>A. nidulans </it>genes to at least one of seven other <it>Aspergillus </it>species: <it>A. niger</it>, <it>A. fumigatus</it>, <it>A. flavus</it>, <it>A. clavatus</it>, <it>A. terreus</it>, <it>A. oryzae </it>and <it>Neosartorya fischeri</it>. GO annotation files compatible with diverse publicly available tools have been generated and deposited online. To further improve their accessibility, we developed a web application for GO enrichment analysis named FetGOat and integrated GO annotations for all <it>Aspergillus </it>species with public genome sequences. Both the annotation files and the web application FetGOat are accessible via the Broad Institute's website (<url>http://www.broadinstitute.org/fetgoat/index.html</url>). To demonstrate the value of those new resources for functional analysis of omics data for the genus <it>Aspergillus</it>, we performed two case studies analyzing microarray data recently published for <it>A. nidulans</it>, <it>A. niger </it>and <it>A. oryzae</it>.</p> <p>Conclusions</p> <p>We mapped <it>A. nidulans </it>GO annotation to seven other <it>Aspergilli</it>. By depositing the newly mapped GO annotation online as well as integrating it into the web tool FetGOat, we provide new, valuable and easily accessible resources for omics data analysis and interpretation for the genus <it>Aspergillus</it>. Furthermore, we have given a general example of how a well annotated genome can help improving GO annotation of related species to subsequently facilitate the interpretation of omics data.</p

Channelized lava flows at the East Pacific Rise crest 9°–10°N : the importance of off-axis lava transport in developing the architecture of young oceanic crust

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 6 (2005): Q08005, doi:10.1029/2005GC000912.Submarine lava flows are the building blocks of young oceanic crust. Lava erupted at the ridge axis is transported across the ridge crest in a manner dictated by the rheology of the lava, the characteristics of the eruption, and the topography it encounters. The resulting lava flows can vary dramatically in form and consequently in their impact on the physical characteristics of the seafloor and the architecture of the upper 50–500 m of the oceanic crust. We have mapped and measured numerous submarine channelized lava flows at the East Pacific Rise (EPR) crest 9°–10°N that reflect the high-effusion-rate and high-flow-velocity end-member of lava eruption and transport at mid-ocean ridges. Channel systems composed of identifiable segments 50–1000 m in length extend up to 3 km from the axial summit trough (AST) and have widths of 10–50 m and depths of 2–3 m. Samples collected within the channels are N-MORB with Mg# indicating eruption from the AST. We produce detailed maps of lava surface morphology across the channel surface from mosaics of digital images that show lineated or flat sheets at the channel center bounded by brecciated lava at the channel margins. Modeled velocity profiles across the channel surface allow us to determine flux through the channels from 0.4 to 4.7 × 103 m3/s, and modeled shear rates help explain the surface morphology variation. We suggest that channelized lava flows are a primary mechanism by which lava accumulates in the off-axis region (1–3 km) and produces the layer 2A thickening that is observed at fast and superfast spreading ridges. In addition, the rapid, high-volume-flux eruptions necessary to produce channelized flows may act as an indicator of the local magma budget along the EPR. We find that high concentrations of channelized lava flows correlate with local, across-axis ridge morphology indicative of an elevated magma budget. Additionally, in locations where channelized flows are located dominantly to the east or west of the AST, the ridge crest is asymmetric, and layer 2A appears to thicken over a greater distance from the AST toward the side of the ridge crest where the channels are located.This work was supported by NSF grant OCE-9819261 (to H.S., M.A.T., and D.J.F.) as well as the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Penzance Endowed Discretionary Fund