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"Robert, Sarah Corbin"
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Rapid and reversible suppression of ALT by DAXX in osteosarcoma cells
Many tumors maintain chromosome-ends through a telomerase-independent, DNA-templated mechanism called alternative lengthening of telomeres (ALT). While ALT occurs in only a subset of tumors, it is strongly associated with mutations in the genes
ATRX
and
DAXX
, which encode components of an H3.3 histone chaperone complex. The role of
ATRX
and
DAXX
mutations in potentiating the mechanism of ALT remains incompletely understood. Here we characterize an osteosarcoma cell line, G292, with wild-type
ATRX
but a unique chromosome translocation resulting in loss of DAXX function. While ATRX and DAXX form a complex in G292, this complex fails to localize to nuclear PML bodies. We demonstrate that introduction of wild type
DAXX
suppresses the ALT phenotype and restores the localization of ATRX/DAXX to PML bodies. Using an inducible system, we show that ALT-associated PML bodies are disrupted rapidly following DAXX induction and that ALT is again restored following withdrawal of DAXX.
Journal Article
Saturday Talk
I am thrilled that I am unlikely to ever have to drag myself up to Buckhead, which I consider a suburb, miles away and a far less attractive shopping destination than Atlantic Station. I almost never go shopping in a true suburb and now probably never will again, since just about all the shops I want to visit, both chain stores and independents, are located intown. To everyone's delight, a wonderful stranger, Jake Smith, delivered our wayward pooch. I was sobbing, and couldn't stop hugging Jake. He had taken the time to track us down by calling a couple of numbers on Foster's tags and locating our home. Not many people would have given up part of their Saturday to reunite a pet with its owners. While air travel may be more efficient or even necessary in certain situations, daily commuting should not be one of them. Since a Robinson R44 burns 13.5 gallons of fuel an hour, a round-trip hourlong flight is the equivalent of a 216-mile commute in an SUV getting 16 mpg. A year (235 days) of heli-commuting equates to more than 100,000 miles in a Honda Civic getting 32 mpg.
Newspaper Article
Fitness Measures and Health Outcomes in Youth
Physical fitness affects our ability to function and be active.At poor levels, it is associated with such health outcomes as diabetes and cardiovascular disease.Physical fitness testing in American youth was established on a large scale in the 1950s with an early focus on performance-related fitness that gradually gave way to an emphasis on.
eBook
Prophylactic treatment of age-related macular degeneration report number 2: 810-nanometer laser to eyes with drusen: bilaterally eligible patients
To determine the prophylactic and therapeutic value of a single subthreshold 810-nanometer laser treatment in patients with high risk drusen as a manifestation of dry age-related macular degeneration in both eyes.
The Prophylactic Treatment of Age-related Macular Degeneration study enrolled 1,278 eyes of 639 participants who were 50 years or older with at least 5 drusen 63 microm or more in diameter in each eye. Treatment consisted of the placement of an annular grid of 48 extrafoveal, subthreshold 810-nm diode laser applications centered at but sparing the foveola in one eye of each participant, with the fellow eye serving as a control. Development of choroidal neovascularization and change in best-corrected visual acuity were compared between treated and untreated eyes.
Subthreshold laser treatment did not decrease the incidence of choroidal neovascularization in treated versus untreated eyes. A modest visual acuity benefit in treated eyes was found at 24 months (1.5 letter difference; P = .04) and in the treated eyes of participants with a baseline visual acuity between 20/32 and 20/63 (4.0 letter difference; P = .0034). However, this treatment effect was not sustained at 3 years.
A single subthreshold 810-nanometer laser treatment to eyes of participants with bilateral high risk drusen is not an effective prophylactic strategy against choroidal neovascularization.
Journal Article
Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and potential mechanisms for liver-stage differentiation
Plasmodium vivax is the key obstacle to malaria elimination in Asia and Latin America, largely attributed to its ability to form resilient hypnozoites (sleeper-cells) in the host liver that escape treatment and cause relapsing infections. The decision to form hypnozoites is made early in the liver infection and may already be set in sporozoites prior to invasion. To better understand these early stages of infection, we undertook a comprehensive transcriptomic and histone epigenetic characterization of P. vivax sporozoites. The salivary-gland sporozoite transcriptome is heavily composed of transcripts associated with functions needed for early infection of the vertebrate host and development within hepatocytes. Through comparisons to recently published proteome data for the P. vivax sporozoite, our study finds that although highly transcribed, these transcripts are not detectable as proteins and may be regulated through translational repression; a finding we test for a small subset of transcripts and proteins through immunofluorescent microscopy of sporozoites and liver stages in humanized mice. We identify differential transcription between the sporozoite and published transcriptomes of asexual blood-stages and mixed versus hypnozoite-enriched liver stages. These comparisons point to multiple layers of transcriptional, post-transcriptional and post-translational control that appear active in sporozoites and to a lesser extent hypnozoites, but largely absent in replicating liver schizonts or mixed blood-stages. Common transcripts up-regulated in sporozoites and hypnozoites compared to mixed (i.e., schizont) liver-stages identify genes linked to dormancy/persistence in bacteria, amoebae and plants. We also characterise histone epigenetic modifications in the P. vivax sporozoite and explore their role in regulating transcription. Collectively, these data support the hypothesis that the sporozoite as a tightly programmed stage primed to infect the human host and identifies potential mechanisms for hypnozoite-formation that may be further explored in liver stage models.
Paper