G-quadruplex structures mark human regulatory chromatin

G-quadruplex (G4) structural motifs have been linked to transcription, replication and genome instability and are implicated in cancer and other diseases. However, it is crucial to demonstrate the bona fide formation of G4 structures within an endogenous chromatin context. Herein we address this through the development of G4 ChIP-seq, an antibody-based G4 chromatin immunoprecipitation and high-throughput sequencing approach. We find ∼10,000 G4 structures in human chromatin, predominantly in regulatory, nucleosome-depleted regions. G4 structures are enriched in the promoters and 5' UTRs of highly transcribed genes, particularly in genes related to cancer and in somatic copy number amplifications, such as $\textit{MYC}$. Strikingly, $\textit{de novo}$ and enhanced G4 formation are associated with increased transcriptional activity, as shown by HDAC inhibitor-induced chromatin relaxation and observed in immortalized as compared to normal cellular states. Our findings show that regulatory, nucleosome-depleted chromatin and elevated transcription shape the endogenous human G4 DNA landscape.European Molecular Biology Organization (EMBO Long-Term Fellowship), University of Cambridge, Cancer Research UK (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z

Time series of tritium, stable isotopes and chloride reveal short-term variations in groundwater contribution to a stream

A major limitation to the assessment of catchment transit time (TT) stems from the use of stable isotopes or chloride as hydrological tracers, because these tracers are blind to older contributions. Yet, accurately capturing the TT of the old water fraction is essential, as is the assessment of its temporal variations under non-stationary catchment dynamics. In this study we used lumped convolution models to examine time series of tritium, stable isotopes and chloride in rainfall, streamwater and groundwater of a catchment located in subtropical Australia. Our objectives were to determine the different contributions to streamflow and their variations over time, and to understand the relationship between catchment TT and groundwater residence time. Stable isotopes and chloride provided consistent estimates of TT in the upstream part of the catchment. A young component to streamflow was identified that was partitioned into quickflow (mean TT  ≈  2 weeks) and discharge from the fractured igneous rocks forming the headwaters (mean TT  ≈  0.3 years). The use of tritium was beneficial for determining an older contribution to streamflow in the downstream area. The best fits between measured and modelled tritium activities were obtained for a mean TT of 16–25 years for this older groundwater component. This was significantly lower than the residence time calculated for groundwater in the alluvial aquifer feeding the stream downstream ( ≈  76–102 years), emphasising the fact that water exiting the catchment and water stored in it had distinctive age distributions. When simulations were run separately on each tritium streamwater sample, the TT of old water fraction varied substantially over time, with values averaging 17 ± 6 years at low flow and 38 ± 15 years after major recharge events. This counterintuitive result was interpreted as the flushing out of deeper, older waters shortly after recharge by the resulting pressure wave propagation. Overall, this study shows the usefulness of collecting tritium data in streamwater to document short-term variations in the older component of the TT distribution. Our results also shed light on the complex relationships between stored water and water in transit, which are highly non-linear and remain poorly understood

Assessment of interactions between alluvial, Great Artesian Basin (GAB) and volcanic aquifers using 3D visualisation and environmental tracers, Lockyer Valley, southeast Queensland, Australia

A detailed 3D lithological model framework was developed using GOCAD software to understand interactions between alluvial, volcanic and GAB aquifers and the spatial and temporal distribution of groundwater recharge to the alluvium of the Lockyer Valley. Groundwater chemistry, isotope data (H20-δ2H and δ18O , 87Sr/86Sr, 3H and 14C) and groundwater level time-series data from approximately 550 observation wells were integrated into the catchment-wide 3D model to assess the recharge processes involved. This approach enabled the identification of zones where recharge to the alluvium primarily occurs from stream water during episodic flood events. Importantly, the study also demonstrates that in some sections of the alluvium recharge is also from storm rainfall and seepage discharge from the underlying GAB aquifers. These other sources of recharge are indicated by (a) the absence of a response of groundwater levels to flooding in some areas, (b) old radiocarbon ages, and (c) distinct bedrock water chemistry and δ2H and δ18O signatures in alluvial groundwater at these locations. Integration of isotopes, water chemistry and time-series displays of groundwater levels before and after the 2010/2011 flood into the 3D model suggest that the spatial variations in the alluvial groundwater response are mostly controlled by valley morphology and lithological (i.e. permeability) variations within the alluvium. Examination of the groundwater level variations in the 3D model also enabled quantification of the volumetric change of groundwater stored in the unconfined alluvial aquifer prior to and post-flood events

Groundwater mean residence times of a subtropical barrier sand island

Fresh groundwater on barrier islands is affected by changing sea levels and precipitation variability due to climate change and is also vulnerable to anthropogenic processes, such as contamination and groundwater over-abstraction. Constraining groundwater mean residence times (MRTs) and flow paths is essential for understanding and managing these resources. This study uses tritium (H) and carbon-14 (C) to determine the MRTs of groundwater along a transect across subtropical North Stradbroke Island, south-east Queensland, Australia. Hydraulic properties, major ion geochemistry and stable isotopes are used to validate residence times and to identify the processes responsible for their variability. H activities range from less than 0.01 to 1 TU (tritium units), which are values lower than those of local average rainfall (1.6-2.0 TU). C concentrations range from 62.5 to 111pMC (percent modern carbon). Estimated MRTs determined using lumped parameter models and H activities range from 37 to more than 50 years. Recharge occurs over the entire island, and groundwater MRTs generally increase vertically and laterally towards the coastal discharge areas, although no systematic pattern is observed. MRTs estimated from C concentrations display similar spatial relationships but have a much greater range (from modern to approximately 5000 years). Water diversion and retention by lowerpermeability units in the unsaturated parts of the dune systems are the most likely course for relatively long MRTs to date. The results indicate that the internal structures within the dune systems increase MRTs in the groundwater system and potentially divert flow paths. The structures produce perched aquifer systems that are wide-spread and have a significant influence on regional recharge. The geochemical composition of groundwater remains relatively consistent throughout the island, with the only irregularities attributed to old groundwater stored within coastal peat. The outcomes of this study enhance the understanding of groundwater flow, recharge diversion and inhibition for large coastal sand masses in general, especially for older sand masses that have developed structures from pedogenesis and dune movement.With respect to south-east Queensland, it allows the existing regional groundwater flow model to be refined by incorporating independent MRTs to test models' validity. The location of this large fresh groundwater reservoir, in dry and populous south-east Queensland, means that its potential to be used as a water source is always high. Background information on aquifer distribution and groundwater MRTs is crucial to better validate impact assessment for water abstraction

On clustering and polyrepresentation

Polyrepresentation is one of the most prominent principles in a cognitive approach to interactive information seeking and retrieval. When it comes to interactive retrieval, clustering is another method for accessing information. While polyrepresentation has been explored and validated in a scenario where a system returns a ranking of documents, so far there are no insights if and how polyrepresentation and clustering can be combined. In this paper we discuss how both are related and present an approach to integrate polyrepresentation into clustering. We further report some initial evaluation results