When Szent-Gyorgyi called water the “matrix of life”,1 he was echoing an old sentiment. Paracelsus in the 16th century said that “water was the matrix of the world and of all its creatures.”2 But Paracelsus’s notion of a matrixsan active substance imbued with fecund, life-giving propertiess was quite different from the picture that, until very recently, molecular biologists have tended to hold of water’s role in the chemistry of life. Although acknowledging that liquid water has some unusual and important physical and chemical propertiessits potency as a solvent, its ability to form hydrogen bonds, its amphoteric naturesbiologists have regarded it essentially as the backdrop on which life’s molecular components are arrayed. It used to be common practice, for example, to perform computer simulations of biomolecules in a vacuum. Partly this was because the computational intensity of simulating a polypeptide chain was challenging even without accounting for solvent molecules too, but it also reflected the prevailing notion that water does little more than temper or moderate the basic physicochemical interactions responsible for molecular biology. What Gerstein and Levitt said 9 years ago remains true today: “When scientists publish models of biological molecules in journals, they usually draw their models in bright colors and place them against a plain, black background”.3 Curiously, this neglect of water as an active component of the cell went hand in hand with the assumption that life could not exist without it. That was basically an empirical conclusion derived from our experience of life on Earth: environments without liquid water cannot sustain life, and special strategies are needed to cope with situations in which, because of extremes of either heat or cold, the liquid is scarce.4-6 The recent confirmation that there is at least one world rich in organic molecules on which rivers and perhaps shallow seas or bogs are filled with nonaqueous fluidsthe liquid hydrocarbons of Titan7smight now bring some focus, even urgency, to the question of whether water is indeed a * E-mail: p.ball@nature.com. Philip Ball is a science writer and a consultant editor for Nature, where he worked as an editor for physical sciences for more than 10 years. He holds a Ph.D. in physics from the University of Bristol, where he worked on the statistical mechanics of phase transitions in the liquid state. His book H2O: A Biography of Water (Weidenfeld & Nicolson, 1999) was a survey of the current state of knowledge about the behavior of water in situations ranging from planetary geomorphology to cell biology. He frequently writes about aspects of water science for both the popular and the technical media.

https://www.philipball.co.uk/images/stories/docs/pdf/ChemRev_final.pdf

Water as an Active Constituent in Cell Biology

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

The politics of life itself Biomedicine, power, and subjectivity in the twenty-first century

Surface nanobubbles are nanoscopic gaseous domains on immersed substrates which can survive for days. They were first speculated to exist about 20 years ago, based on stepwise features in force curves between two hydrophobic surfaces, eventually leading to the first atomic force microscopy (AFM) image in 2000. While in the early years it was suspected that they may be an artifact caused by AFM, meanwhile their existence has been confirmed with various other methods, including through direct optical observation. Their existence seems to be paradoxical, as a simple classical estimate suggests that they should dissolve in microseconds, due to the large Laplace pressure inside these nanoscopic spherical-cap-shaped objects. Moreover, their contact angle (on the gas side) is much smaller than one would expect from macroscopic counterparts. This review will not only give an overview on surface nanobubbles, but also on surface nanodroplets, which are nanoscopic droplets (e.g., of oil) on (hydrophobic) substrates immersed in water, as they show similar properties and can easily be confused with surface nanobubbles and as they are produced in a similar way, namely, by a solvent exchange process, leading to local oversaturation of the water with gas or oil, respectively, and thus to nucleation. The review starts with how surface nanobubbles and nanodroplets can be made, how they can be observed (both individually and collectively), and what their properties are. Molecular dynamic simulations and theories to account for the long lifetime of the surface nanobubbles are then reported on. The crucial element contributing to the long lifetime of surface nanobubbles and nanodroplets is pinning of the three-phase contact line at chemical or geometric surface heterogeneities. The dynamical evolution of the surface nanobubbles then follows from the diffusion equation, Laplace’s equation, and Henry’s law. In particular, one obtains stable surface nanobubbles when the gas influx from the gas-oversaturated water and the outflux due to Laplace pressure balance. This is only possible for small enough surface bubbles. It is therefore the gas or oil oversaturation ζ that determines the contact angle of the surface nanobubble or nanodroplet and not the Young equation. The review also covers the potential technological relevance of surface nanobubbles and nanodroplets, namely, in flotation, in (photo)catalysis and electrolysis, in nanomaterial engineering, for transport in and out of nanofluidic devices, and for plasmonic bubbles, vapor nanobubbles, and energy conversion. Also given is a discussion on surface nanobubbles and nanodroplets in a nutshell, including theoretical predictions resulting from it and future directions. Studying the nucleation, growth, and dissolution dynamics of surface nanobubbles and nanodroplets will shed new light on the problems of contact line pinning and contact angle hysteresis on the submicron scale.

/pdf/surface-nanobubbles-and-nanodroplets-17od1qfe93.pdf

Surface nanobubbles and nanodroplets

What is it that makes a profession a profession and assures its members special status? What do professionals need to be able to claim their turf and establish priority over others who interact wit...

The gold standard: the challenge of evidence-based medicine and standardization in health care

Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreover, silencing HSBP8 induced autophagy and caused cell death. Tamoxifen itself induced autophagy in sensitive cells but not in resistant ones, and tamoxifen-resistant cells were sensitive to the induction of autophagy by other drugs. These results may point to an important role for autophagy in the sensitivity to tamoxifen.

https://www.pnas.org/content/pnas/108/5/2058.full.pdf

High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy

Foreward. Biology's Love Affair with the Genome / Russ Altman vii 1. Beyond the Genome / Hallam Stevens and Sarah S. Richardson 1 2. The Postgenomic Genome / Evelyn Fox Keller 9 3. What Toll Pursuit: Affective Assemblages in Genomics and Postgenomics / Mike Fortun 32 4. The Polygenomic Organism / John Dupre 56 5. Machine Learning and Genomic Dimensionality: From Features to Landscapes / Adrian Mackenzie 73 6. Networks: Representations and Tools in Postgenomics / Hallam Stevens 103 7. Valuing Data in Postgenomic Biology: How Data Donation and Curation Practices Challenge the Scientific Publication System / Rachel A. Ankeny and Sabina Leonelli 126 8. From Behavior Genetics to Postgenomics / Aaron Panofsky 150 9. Defining Health Justice in the Postgenomic Era / Catherine Bliss 174 10. The Missing Piece of the Puzzle? Measuring the Environment in the Postgenomic Moment / Sara Shostak and Margot Moinester 192 11. Maternal Bodies in the Postgenomic Order: Gender and the Explanatory Landscape of Epigenetics / Sarah S. Richardson 210 12. Approaching Postgenomics / Hallam Stevens and Sarah S. Richardson 232 Bibliography 243 Contributors 281 Index 287

Postgenomics : perspectives on biology after the genome

Life Out of Sequence: A Data-Driven History of Bioinformatics

The long-ranged attractions between hydrophobic amorphous fluoropolymer surfaces are measured in water with and without dissolved air. An atomic force microscope is used to obtain more than 500 measured jump-in distances, which yields statistically reliable results. It is found that the range of the attraction and its variability is generally significantly decreased in deaerated water as compared to normal, aerated water. However, the range and strength of the attraction in deaerated water remain significantly greater than the van der Waals attraction for this system. The experimental observations are consistent with (1) nanobubbles being primarily responsible for the long-ranged attraction in normal water, (2) nanobubbles not being present in deaerated water when the surfaces are not in contact, and (3) the attraction in the absence of nanobubbles being most probably due to the approach to the separation-induced spinodal cavitation of the type identified by Berard et al. [J. Chem. Phys. 1993, 98, 7236]. ...

Effects of degassing on the long-range attractive force between hydrophobic surfaces in water.

On 20 March 2020, in the midst of the COVID-19 pandemic, the Singapore government released a new app called TraceTogether. Developed by the Ministry of Health, SG United, and GovTech Singapore, the...

/pdf/tracetogether-pandemic-response-democracy-and-technology-3n6bfj6af0.pdf

Hallam Stevens

Papers

High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy

Postgenomics : perspectives on biology after the genome

Life Out of Sequence: A Data-Driven History of Bioinformatics

Effects of degassing on the long-range attractive force between hydrophobic surfaces in water.

TraceTogether: Pandemic Response, Democracy, and Technology