ALBERT

Description: We present results from the KMOS Lens-Amplified Spectroscopic Survey (KLASS), an ESO Very Large Telescope (VLT) large program using gravitational lensing to study the spatially resolved kinematics of 44 star-forming galaxies at 0.6 〈 z 〈 2.3 with a stellar mass of 8.1 〈 log(M⋆/M⊙) 〈 11.0. These galaxies are located behind six galaxy clusters selected from the Hubble Space Telescope Grism Lens-Amplified Survey from Space (GLASS). We find that the majority of the galaxies show a rotating disc, but most of the rotation-dominated galaxies only have a low υ rot/σ0 ratio (median of υrot/σ0 ∼ 2.5). We explore the Tully–Fisher relation by adopting the circular velocity, $V_{mathrm{ circ}}=(upsilon _{mathrm{ rot}}^2+3.4sigma _0^2)^{1/2}$, to account for pressure support. We find that our sample follows a Tully–Fisher relation with a positive zero-point offset of +0.18 dex compared to the local relation, consistent with more gas-rich galaxies that still have to convert most of their gas into stars. We find a strong correlation between the velocity dispersion and stellar mass in the KLASS sample. When combining our data to other surveys from the literature, we see an increase of the velocity dispersion with stellar mass at all redshift. We obtain an increase of υrot/σ0 with stellar mass at 0.5 〈 z 〈 1.0. This could indicate that massive galaxies settle into regular rotating discs before the low-mass galaxies. For higher redshift (z 〉 1), we find a weak increase or flat trend. We find no clear trend between the rest-frame UV clumpiness and the velocity dispersion and υrot/σ0. This could suggest that the kinematic properties of galaxies evolve after the clumps formed in the galaxy disc or that the clumps can form in different physical conditions.

Description: Motivation : Feature selection, identifying a subset of variables that are relevant for predicting a response, is an important and challenging component of many methods in statistics and machine learning. Feature selection is especially difficult and computationally intensive when the number of variables approaches or exceeds the number of samples, as is often the case for many genomic datasets. Results : Here, we introduce a new approach—the Bayesian Ising Approximation (BIA)—to rapidly calculate posterior probabilities for feature relevance in L2 penalized linear regression. In the regime where the regression problem is strongly regularized by the prior, we show that computing the marginal posterior probabilities for features is equivalent to computing the magnetizations of an Ising model with weak couplings. Using a mean field approximation, we show it is possible to rapidly compute the feature selection path described by the posterior probabilities as a function of the L2 penalty. We present simulations and analytical results illustrating the accuracy of the BIA on some simple regression problems. Finally, we demonstrate the applicability of the BIA to high-dimensional regression by analyzing a gene expression dataset with nearly 30 000 features. These results also highlight the impact of correlations between features on Bayesian feature selection. Availability and implementation : An implementation of the BIA in C++, along with data for reproducing our gene expression analyses, are freely available at http://physics.bu.edu/~pankajm/BIACode . Contact : charleskennethfisher@gmail.com or ckfisher@bu.edu or pankajm@bu.edu Supplementary information : Supplementary data are available at Bioinformatics online.

Description: The attainment of strong pharmacological effects with oligonucleotides is hampered by inefficient access of these molecules to their sites of action in the cytosol or nucleus. Attempts to address this problem with lipid or polymeric delivery systems have been only partially successful. Here, we describe a novel alternative approach involving the use of a non-toxic small molecule to enhance the pharmacological effects of oligonucleotides. The compound Retro-1 was discovered in a screen for small molecules that reduce the actions of bacterial toxins and has been shown to block the retrograde trafficking pathway. We demonstrate that Retro-1 can also substantially enhance the effectiveness of antisense and splice switching oligonucleotides in cell culture. This effect occurs at the level of intracellular trafficking or processing and is correlated with increased oligonucleotide accumulation in the nucleus but does not involve the perturbation of lysosomal compartments. We also show that Retro-1 can alter the effectiveness of splice switching oligonucleotides in the in vivo setting. These observations indicate that it is possible to enhance the pharmacological actions of oligonucleotides using non-toxic and non-lysosomotropic small molecule adjuncts.

Description: Contemporary Galactic star formation occurs predominantly within gravitationally unstable, cold, dense molecular gas within supersonic, turbulent, magnetized giant molecular clouds (GMCs). Significantly, because the chemical evolution time-scale and the turbulent eddy-turnover time-scale are comparable at typical GMC conditions, molecules evolve via inherently non-equilibrium chemistry which is strongly coupled to the dynamical evolution of the cloud. Current numerical simulation techniques, which include at most three decades in length-scale, can just begin to bridge the divide between the global dynamical time of supersonic turbulent GMCs, and the thermal and chemical evolution within the thin post-shock cooling layers of their background turbulence. We address this GMC astrochemical scales problem using a solution methodology, which permits both complex three-dimensional turbulent dynamics as well as accurate treatment of non-equilibrium post-shock thermodynamics and chemistry. We present the current methodology in the context of the larger scope of physical processes important in understanding the chemical evolution of GMCs, including gas-phase chemistry, dust grains and surface chemistry, and turbulent heating. We present results of a new Lagrangian verification test for supersonic turbulence. We characterize the evolution of these species according to the dimensionless local post-shock Damköhler number, which quantifies the ratio of the dynamical time in the post-shock cooling flow to the chemical reaction time of a given species. Lastly, we discuss implications of this work to the selection of GMC molecular tracers, and the zeroing of chemical clocks of GMC cores.

Description: As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C 〉 A/G 〉 T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community.

Description: Tc1 mouse model of Down syndrome (DS) is functionally trisomic for ~120 human chromosome 21 (HSA21) classical protein-coding genes. Tc1 mice display features relevant to the DS phenotype, including abnormalities in learning and memory and synaptic plasticity. To determine the molecular basis for the phenotypic features, the levels of 90 phosphorylation-specific and phosphorylation-independent proteins were measured by Reverse Phase Protein Arrays in hippocampus and cortex, and 64 in cerebellum, of Tc1 mice and littermate controls. Abnormal levels of proteins involved in MAP kinase, mTOR, GSK3B and neuregulin signaling were identified in trisomic mice. In addition, altered correlations among the levels of N-methyl-D-aspartate (NMDA) receptor subunits and the HSA21 proteins amyloid beta (A4) precursor protein (APP) and TIAM1, and between immediate early gene (IEG) proteins and the HSA21 protein superoxide dismutase-1 (SOD1) were found in the hippocampus of Tc1 mice, suggesting altered stoichiometry among these sets of functionally interacting proteins. Protein abnormalities in Tc1 mice were compared with the results of a similar analysis of Ts65Dn mice, a DS mouse model that is trisomic for orthologs of 50 genes trisomic in the Tc1 plus an additional 38 HSA21 orthologs. While there are similarities, abnormalities unique to the Tc1 include increased levels of the S100B calcium-binding protein, mTOR proteins RAPTOR and P70S6, the AMP-kinase catalytic subunit AMPKA, the IEG proteins FBJ murine osteosarcoma viral oncogene homolog (CFOS) and activity-regulated cytoskeleton-associated protein (ARC), and the neuregulin 1 receptor ERBB4. These data identify novel perturbations, relevant to neurological function and to some seen in Alzheimer's disease, that may occur in the DS brain, potentially contributing to phenotypic features and influencing drug responses.

Description: Zinc finger motifs are distributed amongst many eukaryotic protein families, directing nucleic acid–protein and protein–protein interactions. Zinc finger protein 106 (ZFP106) has previously been associated with roles in immune response, muscle differentiation, testes development and DNA damage, although little is known about its specific function. To further investigate the function of ZFP106, we performed an in-depth characterization of Zfp106 deficient mice ( Zfp106 –/– ), and we report a novel role for ZFP106 in motor and sensory neuronal maintenance and survival. Zfp106 –/– mice develop severe motor abnormalities, major deficits in muscle strength and histopathological changes in muscle. Intriguingly, despite being highly expressed throughout the central nervous system, Zfp106 –/– mice undergo selective motor and sensory neuronal and axonal degeneration specific to the spinal cord and peripheral nervous system. Neurodegeneration does not occur during development of Zfp106 –/– mice, suggesting that ZFP106 is likely required for the maintenance of mature peripheral motor and sensory neurons. Analysis of embryonic Zfp106 –/– motor neurons revealed deficits in mitochondrial function, with an inhibition of Complex I within the mitochondrial electron transport chain. Our results highlight a vital role for ZFP106 in sensory and motor neuron maintenance and reveal a novel player in mitochondrial dysfunction and neurodegeneration.

Description: Recent research on the relationship between coral reef water temperature and fish swimming activity has stated that swimming speed is inversely correlated with temperature above a species' optimum temperature (Johansen, J. L., and Jones, G. P. 2011. Increasing ocean temperature reduces the metabolic performance and swimming ability of coral reef damselfishes. Global Change Biology, 17: 2971–2979; Johansen, J. L., Messmer,V., Coker, D. J., Hoey, A. S., and Pratchett, M. S. 2014. Increasing ocean temperatures reduce activity patterns of a large commercially important coral reef fish. Global Change Biology, 20: 1067–1074). For tropical coral reefs, one anticipated consequence of global warming is an increase of ≥3°C in average water temperature in addition to greater thermal fluctuations [IPCC (Intergovernmental Panel on Climate Change). 2007. Summary for policymakers. In Climate Change 2007: The Physical Science Basis. Contribution of Working, Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. Ed. by S. Solomon, D. Qin, and M. Manning et al. Cambridge University Press, Cambridge, UK; Lough, J. 2007. Climate and climate change on the Great Barrier Reef. In Climate Change and the Great Barrier Reef. Ed. by J. Johnson and P. A. Marshall, pp. 15–50. Great Barrier Reef Marine Park Authority and Australian Greenhouse Office, Townsville, Qld, Australia; Johansen and Jones, 2011]. Evaluating the behaviour of coral reef associated fish species at different temperatures can help to assess their sensitivity to climate change. In this study, the speed of freely swimming fish in a natural setting is investigated as a function of seasonal changes in water temperature, as contrasted with systematic temperature increases in a fish tank. We show that Dascyllus reticulatus swim faster as a function of increased water temperature over the range 20.9–30.3°C. The experiments were carried out using ~3.6 million fish trajectories observed at the Kenting National Park in Taiwan. Fish speed was computed by detecting and tracking the fish through consecutive video frames, then converting image speeds to scene speeds. Temperatures were grouped into 10 intervals. The data reveal an ~2 mm s –1 increase in average speed per additional temperature degree over the range of 20.9–30.3°C. The Mann–Kendall test using the mean and median speed for each interval revealed that there is a speed increase trend as temperature increases at the 0.05 significance level, rather than a random increase. Our results complement previous studies that investigated the effect of temperature on the swimming performance of different fish species in the laboratory (Johansen and Jones, 2011; Myrick, C. A. and Cech, J. J. 2000. Swimming performance of four California stream fishes: temperature effects. Environmental Biology of Fishes, 58: 289–295; Ojanguren, A. F. and Braña, F. 2000. Thermal dependence of swimming endurance in juvenile brown trout. Journal of Fish Biology, 56: 1342–1347; Lough 2007; Johansen et al ., 2014).