Locked nucleic acid: tighter is different

This viewpoint briefly reviews the impact of Locked Nucleic Acid (LNA) oligonucleotides, first described in a ChemComm paper in 1998. A number of unique applications in oligonucleotide biotechnology have been made possible by the high binding affinity and specificity of LNA, and these provide the main focus of the viewpoint

Silencing disease genes in the laboratory and the clinic

Synthetic nucleic acids are commonly used laboratory tools for modulating gene expression and have the potential to be widely used in the clinic. Progress towards nucleic acid drugs, however, has been slow and many challenges remain to be overcome before their full impact on patient care can be understood. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression. We first describe these two approaches and contrast their relative strengths and weaknesses for laboratory applications. We then review the choices faced during development of clinical candidates and the current state of clinical trials. Attitudes towards clinical development of nucleic acid silencing strategies have repeatedly swung from optimism to depression during the past 20 years. Our goal is to provide the information needed to design robust studies with oligonucleotides, making use of the strengths of each oligonucleotide technology

Planning to Write a China Book? Just Say No

We wrote to Jonathan Watts to ask him to write a commentary on the book tour he’s been on to promote When a Billion Chinese Jump, which included a stop at UC Irvine, but he said he was too busy being whisked from champagne receptions to meetings with Hollywood directors seeking to buy the film rights to the book to craft something suitable. Watts was, however, good enough to offer us permission to run (in slightly trimmed-down form) a piece he wrote—with tongue firmly in cheek—for a 2009 issue of the newsletter of the Beijing Foreign Correspondents’ Club. Composed while he was working on When a Billion Chinese Jump, it explores all the reasons why a journalist should resist the siren call of writing a China book

Flame Propagation on the Surfaces of Rapidly Rotating Neutron Stars during Type I X-ray Bursts

We present the first vertically resolved hydrodynamic simulations of a laterally propagating, deflagrating flame in the thin helium ocean of a rotating accreting neutron star. We use a new hydrodynamics solver tailored to deal with the large discrepancy in horizontal and vertical length scales typical of neutron star oceans, and which filters out sound waves that would otherwise limit our timesteps. We find that the flame moves horizontally with velocities of order $10^5$ cm s$^{-1}$, crossing the ocean in few seconds, broadly consistent with the rise times of Type I X-ray bursts. We address the open question of what drives flame propagation, and find that heat is transported from burning to unburnt fuel by a combination of top-to-bottom conduction and mixing driven by a baroclinic instability. The speed of the flame propagation is therefore a sensitive function of the ocean conductivity and spin: we explore this dependence for an astrophysically relevant range of parameters and find that in general flame propagation is faster for slower rotation and higher conductivity.Comment: Accepted for publication by MNRA

Rotational effects in thermonuclear Type I Bursts: equatorial crossing and directionality of flame spreading

In a previous study on thermonuclear (type I) nursts on accreting neutron stars we addressed and demonstrated the importance of the effects of rotation, through the Coriolis force, on the propagation of the burning flame. However, that study only analysed cases of longitudinal propagation, where the Coriolis force coefficient $2\Omega\cos\theta$ was constant. In this paper, we study the effects of rotation on propagation in the meridional (latitudinal) direction, where the Coriolis force changes from its maximum at the poles to zero at the equator. We find that the zero Coriolis force at the equator, while affecting the structure of the flame, does not prevent its propagation from one hemisphere to another. We also observe structural differences between the flame propagating towards the equator and that propagating towards the pole, the second being faster. In the light of the recent discovery of the low spin frequency of burster IGR~J17480-2446 rotating at 11 Hz (for which Coriolis effects should be negligible) we also extend our simulations to slow rotation.Comment: Accepted for publication by MNRA

Fast and slow magnetic deflagration fronts in Type I X-ray bursts

Type I X-ray bursts are produced by thermonuclear runaways that develop on accreting neutron stars. Once one location ignites, the flame propagates across the surface of the star. Flame propagation is fundamental in order to understand burst properties like rise time and burst oscillations. Previous work quantified the effects of rotation on the front, showing that the flame propagates as a deflagration and that the front strongly resembles a hurricane. However the effect of magnetic fields was not investigated, despite the fact that magnetic fields strong enough to have an effect on the propagating flame are expected to be present on many bursters. In this paper we show how the coupling between fluid layers introduced by an initially vertical magnetic field plays a decisive role in determining the character of the fronts that are responsible for the Type I bursts. In particular, on a star spinning at 450 Hz (typical among the bursters) we test seed magnetic fields of $10^{7} - 10^{10}$ G and find that for the medium fields the magnetic stresses that develop during the burst can speed up the velocity of the burning front, bringing the simulated burst rise time close to the observed values. By contrast, in a magnetic slow rotator like IGR J17480--2446, spinning at 11 Hz, a seed field $\gtrsim 10^9$ G is required to allow localized ignition and the magnetic field plays an integral role in generating the burst oscillations observed during the bursts.Comment: Pubblished on MNRA

Probabilistic estimates of climate change impacts on UK water resources

Climate change will increase temperatures and change rainfall across the UK. In turn, this will modify patterns of river flow and groundwater recharge, affecting the availability of water. There have been many studies of the impact of climate change on river flows in the UK, but coverage has been uneven and methods have varied. Consequently, it has been very difficult to compare different locations and hard to identify appropriate adaptation responses

Spatiotemporal Changes in Nuclear Strain Measured by Traction Force Microscopy

The knowledge of how cells interact with and sense their surroundings is missing the key components of time dependency and how substrate stiffness affects amount and rate of strain. This new knowledge of cell-substrate interaction can be applied further to research regarding chromatin spatiotemporal dynamics to better understand gene accessibility for transcription. Studying how the cell functions on a deeper level will provide understanding of cellular morphological changes and proliferation. This study uses the methods of optical microscopy and traction force microscopy (TFM) to image substrate deformation as well as analyze its strain profile to find where forces are interacting with the substrate the most. A 60X objective on a confocal microscope was used to image the cell membrane, nucleus, and fluorescent beads in PDMS gels of varying stiffness on which the cells were placed. Based on how the nucleus deforms as well as how the beads move due to cell-substrate interaction, a strain profile of the gel along with traction force analysis can be determined to quantify how the cell is interacting with its substrate. The results are that as the cell is trypsinized after spreading along the substrate, the focal adhesions made by the cell will disconnect, causing the beads to spread out locally around the cell. It was also found that as substrate stiffness increases, the rate of cell spreading increases. From these findings, it can be concluded that the cell responds more positively in environments of higher stiffness and spreads at a faster rate