635 research outputs found
Context Tree Selection: A Unifying View
The present paper investigates non-asymptotic properties of two popular
procedures of context tree (or Variable Length Markov Chains) estimation:
Rissanen's algorithm Context and the Penalized Maximum Likelihood criterion.
First showing how they are related, we prove finite horizon bounds for the
probability of over- and under-estimation. Concerning overestimation, no
boundedness or loss-of-memory conditions are required: the proof relies on new
deviation inequalities for empirical probabilities of independent interest. The
underestimation properties rely on loss-of-memory and separation conditions of
the process.
These results improve and generalize the bounds obtained previously. Context
tree models have been introduced by Rissanen as a parsimonious generalization
of Markov models. Since then, they have been widely used in applied probability
and statistics
Ethylene is involved in pistil fate by modulating the onset of ovule senescence and the GA-mediated fruit set in Arabidopsis
Background: Ovule lifespan is an important factor in determining the ability to set fruits and produce seeds. Once
ovule senescence is established, fruit set capacity in response to gibberellins (GAs) is lost. We aimed to elucidate
whether ethylene plays a role in controlling ovule senescence and the fruit set response in Arabidopsis.
Results: Ethylene response inhibitors, silver thiosulphate (STS) and 1-methylcyclopropene (1-MCP), were able to
delay the loss of pistil response to GA3
. In addition, ethylene insensitive mutants ein2-5 and ein3-1 showed delayed
loss of pistil response, as in plants treated with STS and 1-MCP, while constitutive mutant ctr1-1 displayed
premature loss of response. The analysis of the expression of ethylene biosynthesis genes suggests that ethylene is
synthesised in ovules at the onset of ovule senescence, while a transcriptional meta-analysis also supports an
activated ethylene-dependent senescence upon the establishment of ovule senescence. Finally, a SAG12:GUS
reporter line proved useful to monitor ovule senescence and to directly demonstrate that ethylene specifically
modulates ovule senescence.
Conclusions: We have shown that ethylene is involved in both the control of the ovule lifespan and the
determination of the pistil/fruit fate. Our data support a role of the ovule in modulating the GA response during
fruit set in Arabidopsis. A possible mechanism that links the ethylene modulation of the ovule senescence and the
GA3
-induced fruit set response is discussed.The authors wish to thank Drs. Alonso and Amasino for their gifts of seeds; Drs. Alonso, Alabadi, and Blazquez for critically reading the manuscript, and Ms. Argomaniz and Ms. Fuster for technical assistance in the lab. This work has been supported by grants BIO2005-07156-C02-01 and BIO2008-01039 from the Spanish Ministry of Science and Innovation, Plan Nacional de I+D. PCB received a PhD fellowship from the Spanish Ministry of Science and Innovation.Carbonell Bejerano, P.; Urbez Lagunas, C.; Granell Richart, A.; Carbonell Gisbert, J.; Perez Amador, MA. (2011). Ethylene is involved in pistil fate by modulating the onset of ovule senescence and the GA-mediated fruit set in Arabidopsis. BMC Plant Biology. 11:84-84. https://doi.org/10.1186/1471-2229-11-84S84841
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Evolutionary biology for the 21st century
New theoretical and conceptual frameworks are required for evolutionary biology to capitalize on the wealth of data now becoming available from the study of genomes, phenotypes, and organisms - including humans - in their natural environments.Molecular and Cellular BiologyOrganismic and Evolutionary Biolog
Optimal Amnesic Probabilistic Automata or How to Learn and Classify Proteins in Linear Time and Space
Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions
© 2019, The Author(s), under exclusive licence to Springer Nature Limited. The cytoskeletal interacting protein Septin 9 (SEPT9), a member of the septin gene family, has been proposed to have oncogenic functions. It is a known hot spot of retroviral tagging insertion and a fusion partner of both de novo and therapy-induced mixed lineage leukemia (MLL). Of all septins, SEPT9 holds the strongest link to cancer, especially breast cancer. Murine models of breast cancer frequently exhibit SEPT9 amplification in the form of double minute chromosomes, and about 20% of human breast cancer display genomic amplification and protein over expression at the SEPT9 locus. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies reveal that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while SEPT9 downregulation inhibits this process. The degradation pattern is peripheral and associated with focal adhesions (FAs), where it is coupled with increased expression of matrix metalloproteinases (MMPs). SEPT9 overexpression induces MMP upregulation in human tumors and in culture models and promotes MMP3 secretion to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filament assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes upregulation and both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.
It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases6-8. This includes muscle biopsies from patients with undiagnosed rare muscle disorders6,9, and cultured fibroblasts from patients with mitochondrial disorders7. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution
The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents
Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents
Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences
(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Components of genetic associations across 2,138 phenotypes in the UK Biobank highlight adipocyte biology
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