Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer

Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyse 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP and SHQ1) and driver amplifications (AR and MYC). In serial plasma analyses, we observe changes in focal amplifications in 40% of cases. The mean time interval between new amplifications was 26.4 weeks (range: 5–52 weeks), suggesting that they represent rapid adaptations to selection pressure. An increase in neuron-specific enolase is accompanied by clonal pattern changes in the tumour genome, most consistent with subclonal diversification of the tumour. Our findings suggest a high plasticity of prostate cancer genomes with newly occurring focal amplifications as a driving force in progression

Ice nucleation by water-soluble macromolecules

Cloud glaciation is critically important for the global radiation budget (albedo) and for initiation of precipitation. But the freezing of pure water droplets requires cooling to temperatures as low as 235 K. Freezing at higher temperatures requires the presence of an ice nucleator, which serves as a template for arranging water molecules in an ice-like manner. It is often assumed that these ice nucleators have to be insoluble particles. We point out that also free macromolecules which are dissolved in water can efficiently induce ice nucleation: the size of such ice nucleating macromolecules (INMs) is in the range of nanometers, corresponding to the size of the critical ice embryo. As the latter is temperature-dependent, we see a correlation between the size of INMs and the ice nucleation temperature as predicted by classical nucleation theory. Different types of INMs have been found in a wide range of biological species and comprise a variety of chemical structures including proteins, saccharides, and lipids. Our investigation of the fungal species Acremonium implicatum, Isaria farinosa, and Mortierella alpina shows that their ice nucleation activity is caused by proteinaceous water-soluble INMs. We combine these new results and literature data on INMs from fungi, bacteria, and pollen with theoretical calculations to develop a chemical interpretation of ice nucleation and water-soluble INMs. This has atmospheric implications since many of these INMs can be released by fragmentation of the carrier cell and subsequently may be distributed independently. Up to now, this process has not been accounted for in atmospheric models

Ice nucleation by water-soluble macromolecules

Cloud glaciation is critically important for the global radiation budget (albedo) and for initiation of precipitation. But the freezing of pure water droplets requires cooling to temperatures as low as 235 K. Freezing at higher temperatures requires the presence of an ice nucleator, which serves as a template for arranging water molecules in an ice-like manner. It is often assumed that these ice nucleators have to be insoluble particles. We point out that also free macromolecules which are dissolved in water can efficiently induce ice nucleation: the size of such ice nucleating macromolecules (INMs) is in the range of nanometers, corresponding to the size of the critical ice embryo. As the latter is temperature-dependent, we see a correlation between the size of INMs and the ice nucleation temperature as predicted by classical nucleation theory. Different types of INMs have been found in a wide range of biological species and comprise a variety of chemical structures including proteins, saccharides, and lipids. Our investigation of the fungal species Acremonium implicatum, Isaria farinosa, and Mortierella alpina shows that their ice nucleation activity is caused by proteinaceous water-soluble INMs. We combine these new results and literature data on INMs from fungi, bacteria, and pollen with theoretical calculations to develop a chemical interpretation of ice nucleation and water-soluble INMs. This has atmospheric implications since many of these INMs can be released by fragmentation of the carrier cell and subsequently may be distributed independently. Up to now, this process has not been accounted for in atmospheric models

The relevance of nanoscale biological fragments for ice nucleation in clouds

Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles

A marine biogenic source of atmospheric ice nucleating particles

The amount of ice present in clouds can affect cloud lifetime, precipitation and radiative properties1,2. The formation of ice in clouds is facilitated by the presence of airborne ice nucleating particles1,2. Sea spray is one of the major global sources of atmospheric particles, but it is unclear to what extent these particles are capable of nucleating ice3-11. Sea spray aerosol contains large amounts of organic material that is ejected into the atmosphere during bubble bursting at the organically enriched sea-air interface or sea surface microlayer12-19. Here we show that organic material in the sea surface microlayer nucleates ice under conditions relevant for mixed-phase cloud and high-altitude ice cloud formation. The ice nucleating material is likely biogenic and less than ~0.2 μm in size. We find that exudates separated from cells of the marine diatom T. Pseudonana nucleate ice and propose that organic material associated with phytoplankton cell exudates is a likely candidate for the observed ice nucleating ability of the microlayer samples. Global model simulations of marine organic aerosol in combination with our measurements suggest that marine organic material may be an important source of ice nucleating particles in remote marine environments such as the Southern Ocean, North Pacific and North Atlantic

The study of atmospheric ice-nucleating particles via microfluidically generated droplets

Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 10³–10⁶ ambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations. Here, we present the application of microfluidic devices to the study of atmospheric INPs via the simple and rapid production of monodisperse droplets and their subsequent freezing on a cold stage. This device offers the potential for the testing of INP concentrations in aqueous samples with high sensitivity and high counting statistics. Various INPs were tested for validation of the platform, including mineral dust and biological species, with results compared to literature values. We also describe a methodology for sampling atmospheric aerosol in a manner that minimises sampling biases and which is compatible with the microfluidic device. We present results for INP concentrations in air sampled during two field campaigns: (1) from a rural location in the UK and (2) during the UK’s annual Bonfire Night festival. These initial results will provide a route for deployment of the microfluidic platform for the study and quantification of INPs in upcoming field campaigns around the globe, while providing a benchmark for future lab-on-a-chip-based INP studies