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PubMed
Tipping points in open systems: bifurcation, noise-included and rate-dependent examples in the climate system
Philos Trans A Math Phys Eng Sci
PubMed
Alterations to the remote control of Shh gene expression cause congenital abnormalities
Philos Trans R Soc Lond B Biol Sci
Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis-regulators of transcription and may reside at long distances from the genes ...
PubMed
From remote enhancers to gene regulation: charting the genome's regulatory landscapes
Philos Trans R Soc Lond B Biol Sci
Vertebrate genes are characterized by the presence of cis-regulatory elements located at great distances from the genes they control. Alterations of these elements have been implicated in human diseases and evolution, yet little is known about how th...
PubMed
Functional anatomy of distant-acting mammalian enhancers
Philos Trans R Soc Lond B Biol Sci
Transcriptional enhancers are a major class of functional element embedded in the vast non-coding portion of the human genome. Acting over large genomic distances, enhancers play critical roles in the tissue and cell type-specific regulation of genes...
PubMed
Human genetic variation within neural crest enhancers: molecular and phenotypic implications
Philos Trans R Soc Lond B Biol Sci
Developmental gene expression programmes are coordinated by the specialized distal cis-regulatory elements called enhancers, which integrate lineage- and signalling-dependent inputs to guide morphogenesis. In previous work, we characterized the genom...
PubMed
High-resolution analysis of cis-acting regulatory networks at the α-globin locus
Philos Trans R Soc Lond B Biol Sci
We have combined the circular chromosome conformation capture protocol with high-throughput, genome-wide sequence analysis to characterize the cis-acting regulatory network at a single locus. In contrast to methods which identify large interacting re...
PubMed
Expression quantitative trait loci: present and future
Philos Trans R Soc Lond B Biol Sci
The last few years have seen the development of large efforts for the analysis of genome function, especially in the context of genome variation. One of the most prominent directions has been the extensive set of studies on expression quantitative tr...
PubMed
Deconvoluting complex tissues for expression quantitative trait locus-based analyses
Philos Trans R Soc Lond B Biol Sci
Breast cancer genome-wide association studies have pinpointed dozens of variants associated with breast cancer pathogenesis. The majority of risk variants, however, are located outside of known protein-coding regions. Therefore, identifying which gen...
PubMed
Effects of gene regulatory reprogramming on gene expression in human and mouse developing hearts
Philos Trans R Soc Lond B Biol Sci
Lineage-specific regulatory elements underlie adaptation of species and play a role in disease susceptibility. We compared functionally conserved and lineage-specific enhancers by cross-mapping 5042 human and 6564 mouse heart enhancers. Of these, 79 ...
PubMed
Chromatin organization and global regulation of Hox gene clusters
Philos Trans R Soc Lond B Biol Sci
During development, a properly coordinated expression of Hox genes, within their different genomic clusters is critical for patterning the body plans of many animals with a bilateral symmetry. The fascinating correspondence between the topological or...
PubMed
CTCF: the protein, the binding partners, the binding sites and their chromatin loops
Philos Trans R Soc Lond B Biol Sci
CTCF has it all. The transcription factor binds to tens of thousands of genomic sites, some tissue-specific, others ultra-conserved. It can act as a transcriptional activator, repressor and insulator, and it can pause transcription. CTCF binds at chr...
PubMed
Deciphering cis-regulatory control in inflammatory cells
Philos Trans R Soc Lond B Biol Sci
In innate immune system cells, such as macrophages and dendritic cells, deployment of inducible gene expression programmes in response to microbes and danger signals requires highly precise regulatory mechanisms. The inflammatory response has to be t...
PubMed
Regulation from a distance: long-range control of gene expression in development and disease
Philos Trans R Soc Lond B Biol Sci
PubMed
Bevacizumab for the Treatment of Glioblastoma
Clin Med Insights Oncol
Glioblastoma (GBM) or grade IV glioma is the most common primary brain tumor in adults. Standard treatment median overall survival (OS) is only 14–15 months and less than 10% of patients will survive 5 years after diagnosis. There is no standard tr...
PubMed
Evidence for the Presence of 1,3-Dimethylamylamine (1,3-DMAA) in Geranium Plant Materials
Anal Chem Insights
1,3-Dimethylamylamine (1,3-DMAA) is an aliphatic amine with stimulant properties that are reportedly found naturally only in geranium plants (Pelargonium graveolens). The presence of 1,3-DMAA in geranium plants was first reported in a paper published...
PubMed
Global trends and uncertainties in terrestrial denitrification and N(2)O emissions
Philos Trans R Soc Lond B Biol Sci
Soil nitrogen (N) budgets are used in a global, distributed flow-path model with 0.5° × 0.5° resolution, representing denitrification and N(2)O emissions from soils, groundwater and riparian zones for the period 1900–2000 and scenarios for the p...
PubMed
The cycling of organic nitrogen through the atmosphere
Philos Trans R Soc Lond B Biol Sci
Atmospheric organic nitrogen (ON) appears to be a ubiquitous but poorly understood component of the atmospheric nitrogen deposition flux. Here, we focus on the ON components that dominate deposition and do not consider reactive atmospheric gases cont...
PubMed
Consequences of human modification of the global nitrogen cycle
Philos Trans R Soc Lond B Biol Sci
The demand for more food is increasing fertilizer and land use, and the demand for more energy is increasing fossil fuel combustion, leading to enhanced losses of reactive nitrogen (N(r)) to the environment. Many thresholds for human and ecosystem he...
PubMed
Biological nitrogen fixation: rates, patterns and ecological controls in terrestrial ecosystems
Philos Trans R Soc Lond B Biol Sci
New techniques have identified a wide range of organisms with the capacity to carry out biological nitrogen fixation (BNF)—greatly expanding our appreciation of the diversity and ubiquity of N fixers—but our understanding of the rates and control...
PubMed
A chronology of human understanding of the nitrogen cycle(†)
Philos Trans R Soc Lond B Biol Sci
Nitrogen over the ages! It was discovered in the eighteenth century. The following century, its importance in agriculture was documented and the basic components of its cycle were elucidated. In the twentieth century, a process to provide an inexhaus...