20 research outputs found
Earth: Atmospheric Evolution of a Habitable Planet
Our present-day atmosphere is often used as an analog for potentially
habitable exoplanets, but Earth's atmosphere has changed dramatically
throughout its 4.5 billion year history. For example, molecular oxygen is
abundant in the atmosphere today but was absent on the early Earth. Meanwhile,
the physical and chemical evolution of Earth's atmosphere has also resulted in
major swings in surface temperature, at times resulting in extreme glaciation
or warm greenhouse climates. Despite this dynamic and occasionally dramatic
history, the Earth has been persistently habitable--and, in fact,
inhabited--for roughly 4 billion years. Understanding Earth's momentous changes
and its enduring habitability is essential as a guide to the diversity of
habitable planetary environments that may exist beyond our solar system and for
ultimately recognizing spectroscopic fingerprints of life elsewhere in the
Universe. Here, we review long-term trends in the composition of Earth's
atmosphere as it relates to both planetary habitability and inhabitation. We
focus on gases that may serve as habitability markers (CO2, N2) or
biosignatures (CH4, O2), especially as related to the redox evolution of the
atmosphere and the coupled evolution of Earth's climate system. We emphasize
that in the search for Earth-like planets we must be mindful that the example
provided by the modern atmosphere merely represents a single snapshot of
Earth's long-term evolution. In exploring the many former states of our own
planet, we emphasize Earth's atmospheric evolution during the Archean,
Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of
potential atmospheric trajectories into the distant future, many millions to
billions of years from now. All of these 'Alternative Earth' scenarios provide
insight to the potential diversity of Earth-like, habitable, and inhabited
worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook
of Exoplanet
Nicotinic acetylcholine receptors in attention circuitry: the role of layer VI neurons of prefrontal cortex
Mutational mechanisms of amplifications revealed by analysis of clustered rearrangements in breast cancers.
BACKGROUND: Complex clusters of rearrangements are a challenge in interpretation of cancer genomes. Some clusters of rearrangements demarcate clear amplifications of driver oncogenes but others are less well understood. A detailed analysis of rearrangements within these complex clusters could reveal new insights into selection and underlying mutational mechanisms. PATIENTS AND METHODS: Here, we systematically investigate rearrangements that are densely clustered in individual tumours in a cohort of 560 breast cancers. Applying an agnostic approach, we identify 21 hotspots where clustered rearrangements recur across cancers. RESULTS: Some hotspots coincide with known oncogene loci including CCND1, ERBB2, ZNF217, chr8:ZNF703/FGFR1, IGF1R, and MYC. Others contain cancer genes not typically associated with breast cancer: MCL1, PTP4A1, and MYB. Intriguingly, we identify clustered rearrangements that physically connect distant hotspots. In particular, we observe simultaneous amplification of chr8:ZNF703/FGFR1 and chr11:CCND1 where deep analysis reveals that a chr8-chr11 translocation is likely to be an early, critical, initiating event. CONCLUSIONS: We present an overview of complex rearrangements in breast cancer, highlighting a potential new way for detecting drivers and revealing novel mechanistic insights into the formation of two common amplicons
Simulated ablation for detection of cells impacting paracrine signalling in histology analysis
Intra-tumour phenotypic heterogeneity limits accuracy of clinical diagnostics and hampers the efficiency
of anti-cancer therapies. Dealing with this cellular heterogeneity requires adequate understanding of its
sources, which is extremely difficult, as phenotypes of tumour cells integrate hardwired (epi)mutational
differences with the dynamic responses to microenvironmental cues. The later come in form of both
direct physical interactions, as well as inputs from gradients of secreted signalling molecules. Furthermore,
tumour cells can not only receive microenvironmental cues, but also produce them. Despite high
biological and clinical importance of understanding spatial aspects of paracrine signaling, adequate research
tools are largely lacking. Here, a partial differential equation (PDE) based mathematical model is
developed that mimics the process of cell ablation. This model suggests how each cell might contribute
to the microenvironment by either absorbing or secreting diffusible factors, and quantifies the extent to
which observed intensities can be explained via diffusion mediated signalling. The model allows for
the separation of phenotypic responses to signalling gradients within tumour microenvironments from
the combined influence of responses mediated by direct physical contact and hardwired (epi)genetic differences.
The method is applied to a multi-channel immunofluorescence in situ hybridization (iFISH)
stained breast cancer histological specimen and correlations are investigated between: HER2 gene amplification;
HER2 protein expression; and cell interaction with the diffusible microenvironment. This
approach allows partial deconvolution of the complex inputs that shape phenotypic heterogeneity of tumour
cells, and identifies cells that significantly impact gradients of signalling molecules
A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers
Biological and Abiological Sulfate Reduction in Two Northern Australian Proterozoic Basins
Formation of supercontinents linked to increases in atmospheric oxygen
Atmospheric oxygen concentrations in the Earth’s atmosphere rose from negligible levels in the Archaean Era to about 21% in the present day. This increase is thought to have occurred in six steps, 2.65, 2.45, 1.8, 0.6, 0.3 and 0.04 billion years ago, with a possible seventh event identified at 1.2 billion years ago. Here we show that the timing of these steps correlates with the amalgamation of Earth’s land masses into supercontinents. We suggest that the continent–continent collisions required to form supercontinents produced supermountains. In our scenario, these supermountains eroded quickly and released large amounts of nutrients such as iron and phosphorus into the oceans, leading to an explosion of algae and cyanobacteria, and thus a marked increase in photosynthesis, and the photosynthetic production of O2. Enhanced sedimentation during these periods promoted the burial of a high fraction of organic carbon and pyrite, thus preventing their reaction with free oxygen, and leading to sustained increases in atmospheric oxygen