892 research outputs found
Shuttle/spacelab contamination environment and effects handbook
This handbook is intended to assist users of the Spacelab/Space Transportation System by providing contamination environments and effects information that may be of value in planning, designing, manufacturing, and operating a space flight experiment. A summary of available molecular and particulate contamination data on the Space Transportation System and its facilities is presented. Contamination models, contamination effects, and protection methods information are also presented. In addition to contamination, the effects of the space environments at STS altitudes on spacecraft materials are included. Extensive references, bibliographies, and contacts are provided
Novel cell adhesion/migration pathways are predictive markers of HDAC inhibitor resistance in cutaneous T cell lymphoma
BACKGROUND: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy.
METHODS: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks (H3K14/9āÆac, H3K27ac). We correlated significant differences in histone acetylation with gene expression in HDACi-resistant/sensitive CTCL. We extended these findings in additional CTCL patient cohorts (RNA-seq, microarray) and using ELISA in matched CTCL patient plasma.
FINDINGS: Resistant CTCL exhibited high levels of histone acetylation, which correlated with increased expression of 338 genes (FDRāÆ\u3cāÆ0Ā·05), including some novel to CTCL: BIRC5 (anti-apoptotic); RRM2 (cell cycle); TXNDC5, GSTM1 (redox); and CXCR4, LAIR2 (cell adhesion/migration). Several of these, including LAIR2, were elevated pre-treatment in HDACi-resistant CTCL. In CTCL patient plasma (nāÆ=āÆ6), LAIR2 protein was also elevated (pāÆ\u3cāÆ0Ā·01) compared to controls.
INTERPRETATION: This study is the first to connect genome-wide differences in chromatin acetylation and gene expression to HDACi-resistance in primary CTCL. Our results identify novel markers with high pre-treatment expression, such as LAIR2, as potential prognostic and/or predictors of HDACi-resistance in CTCL.
FUNDING: NIH:CA156690, CA188286; NCATS: WU-ICTS UL1 TR000448; Siteman Cancer Center: CA091842
Determining subpopulation methylation profiles from bisulfite sequencing data of heterogeneous samples using DXM
Epigenetic changes, such as aberrant DNA methylation, contribute to cancer clonal expansion and disease progression. However, identifying subpopulation-level changes in a heterogeneous sample remains challenging. Thus, we have developed a computational approach, DXM, to deconvolve the methylation profiles of major allelic subpopulations from the bisulfite sequencing data of a heterogeneous sample. DXM does not require prior knowledge of the number of subpopulations or types of cells to expect. We benchmark DXM\u27s performance and demonstrate improvement over existing methods. We further experimentally validate DXM predicted allelic subpopulation-methylation profiles in four Diffuse Large B-Cell Lymphomas (DLBCLs). Lastly, as proof-of-concept, we apply DXM to a cohort of 31 DLBCLs and relate allelic subpopulation methylation profiles to relapse. We thus demonstrate that DXM can robustly find allelic subpopulation methylation profiles that may contribute to disease progression using bisulfite sequencing data of any heterogeneous sample
Sea anemones may thrive in a high CO2 world
Increased seawater pCO 2, and in turn 'ocean acidification' (OA), is predicted to profoundly impact marine ecosystem diversity and function this century. Much research has already focussed on calcifying reef-forming corals (Class: Anthozoa) that appear particularly susceptible to OA via reduced net calcification. However, here we show that OA-like conditions can simultaneously enhance the ecological success of non-calcifying anthozoans, which not only play key ecological and biogeochemical roles in present day benthic ecosystems but also represent a model organism should calcifying anthozoans exist as less calcified (soft-bodied) forms in future oceans. Increased growth (abundance and size) of the sea anemone (Anemonia viridis) population was observed along a natural CO 2 gradient at Vulcano, Italy. Both gross photosynthesis (P G) and respiration (R) increased with pCO 2 indicating that the increased growth was, at least in part, fuelled by bottom up (CO 2 stimulation) of metabolism. The increase of P G outweighed that of R and the genetic identity of the symbiotic microalgae (Symbiodinium spp.) remained unchanged (type A19) suggesting proximity to the vent site relieved CO 2 limitation of the anemones' symbiotic microalgal population. Our observations of enhanced productivity with pCO 2, which are consistent with previous reports for some calcifying corals, convey an increase in fitness that may enable non-calcifying anthozoans to thrive in future environments, i.e. higher seawater pCO 2. Understanding how CO 2-enhanced productivity of non- (and less-) calcifying anthozoans applies more widely to tropical ecosystems is a priority where such organisms can dominate benthic ecosystems, in particular following localized anthropogenic stress. Ā© 2012 Blackwell Publishing Ltd
Genome-wide transcriptome and physiological analyses provide new insights into peanut drought response mechanisms
Drought is one of the main constraints in peanut production in West Texas and eastern New Mexico
regions due to the depletion of groundwater. A multi-seasonal phenotypic analysis of 10 peanut
genotypes revealed C76-16 (C-76) and Valencia-C (Val-C) as the best and poor performers under deficit
irrigation (DI) in West Texas, respectively. In order to decipher transcriptome changes under DI, RNAseq
was performed in C-76 and Val-C. Approximately 369 million raw reads were generated from 12
different libraries of two genotypes subjected to fully irrigated (FI) and DI conditions, of which ~329
million (90.2%) filtered reads were mapped to the diploid ancestors of peanut. The transcriptome
analysis detected 4,508 differentially expressed genes (DEGs), 1554 genes encoding transcription
factors (TFs) and a total of 514 single nucleotide polymorphisms (SNPs) among the identified DEGs.
The comparative analysis between the two genotypes revealed higher and integral tolerance in C-76
through activation of key genes involved in ABA and sucrose metabolic pathways. Interestingly, one
SNP from the gene coding F-box protein (Araip.3WN1Q) and another SNP from gene coding for the lipid
transfer protein (Aradu.03ENG) showed polymorphism in selected contrasting genotypes. These SNPs
after further validation may be useful for performing early generation selection for selecting drought responsive
genotypes
Masting by Eighteen New Zealand Plant Species: The Role of Temperature as a Synchronizing Cue
Masting, the intermittent production of large flower or seed crops by a population of perennial plants, can enhance the reproductive success of participating plants and drive fluctuations in seed-consumer populations and other ecosystem components over large geographic areas. The spatial and taxonomic extent over which masting is synchronized can determine its success in enhancing individual plant fitness as well as its ecosystem-level effects, and it can indicate the types of proximal cues that enable reproductive synchrony. Here, we demonstrate high intra- and intergeneric synchrony in mast seeding by 17 species of New Zealand plants from four families across \u3e150000 km2. The synchronous species vary ecologically (pollination and dispersal modes) and are geographically widely separated, so intergeneric synchrony seems unlikely to be adaptive per se. Synchronous fruiting by these species was associated with anomalously high temperatures the summer before seedfall, a cue linked with the La NinĢa phase of El NinĢoāSouthern Oscillation. The lone asynchronous species appears to respond to summer temperatures, but with a 2-yr rather than 1-yr time lag. The importance of temperature anomalies as cues for synchronized masting suggests that the timing and intensity of masting may be sensitive to global climate change, with widespread effects on taxonomically disparate plant and animal communities
Masting by Eighteen New Zealand Plant Species: The Role of Temperature as a Synchronizing Cue
Observation of stress corrosion cracking using real-time in situ high-speed atomic force microscopy and correlative techniques
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