Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence

Fossil organic carbon utilization in marine Arctic fjord sediments by subsurface micro-organisms

Rock-derived or petrogenic organic carbon has traditionally been regarded as being non-bioavailable and bypassing the active carbon cycle when eroded. However, it has become apparent that this organic carbon might not be so inert, especially in fjord systems where petrogenic organic carbon influxes can be high, making its degradation another potential source of greenhouse gas emissions. The extent to which subsurface micro-organisms use this organic carbon is not well constrained, despite its potential impacts on global carbon cycling. Here, we performed compound-specific radiocarbon analyses on intact polar lipid–fatty acids of live micro-organisms from marine sediments in Hornsund Fjord, Svalbard. By this means, we estimate that local bacterial communities utilize between 5 ± 2% and 55 ± 6% (average of 25 ± 16%) of petrogenic organic carbon for their biosynthesis, providing evidence for the important role of petrogenic organic carbon as a substrate after sediment redeposition. We hypothesize that the lack of sufficient recently synthesized organic carbon from primary production forces micro-organisms into utilization of petrogenic organic carbon as an alternative energy source. The input of petrogenic organic carbon to marine sediments and subsequent utilization by subsurface micro-organisms represents a natural source of fossil greenhouse gas emissions over geological timescale

Genomic Analyses of Breast Cancer Progression Reveal Distinct Routes of Metastasis Emergence

A main controversy in cancer research is whether metastatic abilities are present in the most advanced clone of the primary tumor or result from independently acquired aberrations in early disseminated cancer cells as suggested by the linear and the parallel progression models, respectively. The genetic concordance between different steps of malignant progression is mostly unexplored as very few studies have included cancer samples separated by both space and time. We applied whole exome sequencing and targeted deep sequencing to 26 successive samples from six patients with metastatic estrogen receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis

Современное состояние и перспективы развития ООПТ Томской области

В работе дана характеристика сети особо охраняемых природных территорий Томской области, ее роли в поддержании эколого-хозяйственного баланса области. Определены этапы формирования сети ООПТ. Дан анализ географического разнообразия сети ООПТ и представленности ее в административных районах области. Определена роль сети ООПТ в сохранении редких и исчезающих видов растений и животных. Разработана и реализована методика комплексной оценки эффективности сети ООПТ. Предложены пути ее развития и оптимизации.In work the characteristic of the network of specially protected natural territories of the Tomsk region, its role in maintaining ecological and economic balance of the region. The stages of forming a network of protected areas. The analysis of the geographic diversity of the PA network and its representation in the administrative districts of the region. Defined the role of the network of protected areas in the conservation of rare and endangered species of plants and animals. Developed and implemented a methodology of comprehensive evaluation of the effectiveness of the PA network. The proposed ways of its development and optimization

First implementation of a new cross-disciplinary observation strategy for heavy precipitation events from formation to flooding

Heavy Precipitation Events (HPE) are the result of enormous quantities of water vapor being transported to a limited area. HPE rainfall rates and volumes cannot be fully stored on and below the land surface, often leading to floods with short forecast lead times that may cause damage to humans, properties, and infrastructure. Toward an improved scientific understanding of the entire process chain from HPE formation to flooding at the catchment scale, we propose an elaborated event-triggered observation concept. It combines flexible mobile observing systems out of the fields of meteorology, hydrology and geophysics with stationary networks to capture atmospheric transport processes, heterogeneous precipitation patterns, land surface and subsurface storage processes, and runoff dynamics. As part of the Helmholtz Research Infrastructure MOSES (Modular Observation Solutions for Earth Systems), the effectiveness of our observation strategy is illustrated by its initial implementation in the Mueglitz river basin (210 km$^2$), a headwater catchment of the Elbe in the Eastern Ore Mountains with historical and recent extreme flood events. Punctual radiosonde observations combined with continuous microwave radiometer measurements and back trajectory calculations deliver information about the moisture sources, and initiation and development of HPE. X-band radar observations calibrated by ground-based disdrometers and rain gauges deliver precipitation information with high spatial resolution. Runoff measurements in small sub-catchments complement the discharge time series of the operational network of gauging stations. Closing the catchment water balance at the HPE scale, however, is still challenging. While evapotranspiration is of less importance when studying short-term convective HPE, information on the spatial distribution and on temporal variations of soil moisture and total water storage by stationary and roving cosmic ray measurements and by hybrid terrestrial gravimetry offer prospects for improved quantification of the storage term of the water balance equation. Overall, the cross-disciplinary observation strategy presented here opens up new ways toward an integrative and scale-bridging understanding of event dynamics

Surface-controlled reversal of the selectivity of halogen bonds

Intermolecular halogen bonds are ideally suited for designing new molecular assemblies because of their strong directionality and the possibility of tuning the interactions by using different types of halogens or molecular moieties. Due to these unique properties of the halogen bonds, numerous areas of application have recently been identified and are still emerging. Here, we present an approach for controlling the 2D self-assembly process of organic molecules by adsorption to reactive vs. inert metal surfaces. Therewith, the order of halogen bond strengths that is known from gas phase or liquids can be reversed. Our approach relies on adjusting the molecular charge distribution, i.e., the σ-hole, by molecule-substrate interactions. The polarizability of the halogen and the reactiveness of the metal substrate are serving as control parameters. Our results establish the surface as a control knob for tuning molecular assemblies by reversing the selectivity of bonding sites, which is interesting for future applications

Transport of organic carbon from the California coast to the slope region : a study of Δ14C and δ13C signatures of organic compound classes

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 19 (2005): GB2018, doi:10.1029/2004GB002422.Surface sediments along a transect from an abyssal site in the northeastern Pacific (Station M, 34°50′N, 123°00′W) to a small mountainous river on the California coast (Santa Clara River) were studied to investigate the sources and cycling of organic matter on the continental margin. Sediment samples were separated into organic compound fractions (extractable lipids, amino acids (THAA), carbohydrates (TCHO), and the acid-insoluble fraction), and their carbon isotope ratios were measured. The Δ14C values of all the THAA and TCHO fractions were greater than −100‰, indicating relatively modern organic carbon (OC) source(s), and rapid cycling of these fractions. In contrast, the Δ14C values of extractable lipids and the acid-insoluble fraction were distinctly lower than those of the THAA and TCHO fractions. The Δ14C values of source OC to the sediments were estimated using a simple mixed layer model. These values were lower than the Δ14C signatures of pre-industrial plankton suggesting input of both old OC and contemporary plankton to the margin sediments. The source of old OC at the 2000-m site was likely from laterally transported coastal sediment. The estimated low Δ14C value of the transported OC suggests that old lipids and acid-insoluble material were selectively transported to the 2000-m site. The contribution of riverine POC to the margin sediments were estimated from Δ14C and δ13C values and indicate that relict OC exported by rivers was an important source of old lipids and acid-insoluble material to sedimentary OC on the shelf.This research was supported by NSF OCE Chemical Oceanography Program and ACS Petroleum Research Fund (to E. R. M. D.), the UCOP Marine Science Fellowship Program (to J. H.), and the Dreyfus Foundation for an Environmental Science Postdoctoral Fellowship grant (to T. K.)

α-Synuclein and DJ-1 as Potential Biological Fluid Biomarkers for Parkinson’s Disease

Parkinson’s disease (PD) is the most common form of movement disorder and affects approximately 4% of the population aged over 80 years old. Currently, PD cannot be prevented or cured, and no single diagnostic biomarkers are available. Notably, recent studies suggest that two familial PD-linked molecules, α-synuclein and DJ-1, are present in cerebrospinal fluid (CSF) and that their levels may be altered during the progression of PD. In this regard, sensitive and accurate methods for evaluation of α-synuclein and DJ-1 levels in the CSF and blood have been developed, and the results suggest that the levels of both molecules are significantly decreased in the CSF in patients with PD compared with age-matched controls. Furthermore, specific detection and quantification of neurotoxic oligometric forms of α-synuclein in the blood using enzyme-linked immunosorbent assays might be expected as potential peripheral biomarkers for PD, although further validation is required. Currently, neither α-synuclein nor DJ-1 is satisfactory as a single biomarker for PD, but combinatory evaluation of these biological fluid molecules with other biomarkers and imaging techniques may provide reliable information for diagnosis of PD