Lake sedimentological and ecological response to hyperthermals : Boltysh impact crater, Ukraine

Acknowledgements Initial drilling of the Boltysh meteorite crater was funded by Natural Environment Research Council (NERC) grant NE/D005043/1. The authors are extremely grateful to the valuable scientific contributions of S. Kelley and I. Gilmour. The constructive and critical reviews by M. Schuster and an anonymous reviewer greatly helped to improve this manuscript.Peer reviewedPostprin

RNA proximity sequencing data and analysis pipeline from a human neuroblastoma nuclear transcriptome.

We have previously developed and described a method for measuring RNA co-locations within cells, called Proximity RNA-seq, which promises insights into RNA expression, processing, storage and translation. Here, we describe transcriptome-wide proximity RNA-seq datasets obtained from human neuroblastoma SH-SY5Y cell nuclei. To aid future users of this method, we also describe and release our analysis pipeline, CloseCall, which maps cDNA to a custom transcript annotation and allocates cDNA-linked barcodes to barcode groups. CloseCall then performs Monte Carlo simulations on the data to identify pairs of transcripts, which are co-barcoded more frequently than expected by chance. Furthermore, derived co-barcoding frequencies for individual transcripts, dubbed valency, serve as proxies for RNA density or connectivity for that given transcript. We outline how this pipeline was applied to these sequencing datasets and openly share the processed data outputs and access to a virtual machine that runs CloseCall. The resulting data specify the spatial organization of RNAs and builds hypotheses for potential regulatory relationships between RNAs

A systematically coarse-grained model for DNA, and its predictions for persistence length, stacking, twist, and chirality

We introduce a coarse-grained model of DNA with bases modeled as rigid-body ellipsoids to capture their anisotropic stereochemistry. Interaction potentials are all physicochemical and generated from all-atom simulation/parameterization with minimal phenomenology. Persistence length, degree of stacking, and twist are studied by molecular dynamics simulation as functions of temperature, salt concentration, sequence, interaction potential strength, and local position along the chain, for both single- and double-stranded DNA where appropriate. The model of DNA shows several phase transitions and crossover regimes in addition to dehybridization, including unstacking, untwisting, and collapse which affect mechanical properties such as rigidity and persistence length. The model also exhibits chirality with a stable right-handed and metastable left-handed helix.Comment: 30 pages, 20 figures, Supplementary Material available at http://www.physics.ubc.ca/~steve/publications.htm

An Association between Head Circumference and Alzheimer's Disease in a Population-Based Study of Aging and Dementia

We investigated the association between head circumference (HC) and Alzheimer's disease (AD) in a cross-sectional population-based study of aging in North Manhattan. Six hundred forty-nine subjects underwent neurologic, neuropsychological, and anthropometric evaluations; apolipoprotein E (apoE) genotype was available for a subsample of 300 individuals. Logistic regression analyses were performed with AD the outcome of interest to evaluate any association between HC and AD. In these analyses, HC evaluated as a continuous variable was associated with AD (OR 0.8, 95% CI 0.7-0.9) after adjusting for age, education, and ethnicity, gender, and height. Analyses suggested that increased risk resided mainly in those with smallest HC. Thus, women whose HC was within the lowest quintile of HC for women were 2.9 (95% CI 1.4-6.1) times more likely to have AD, after adjusting for age, education, and ethnicity; and men in the lowest quintile of HC (for men) were 2.3 times more likely to have AD (95% CI 0.6-9.8). There was no confounding by height, weight, or apoE genotype. The results are consistent with previous studies that suggest that premorbid brain size may influence the age-specific risk for AD. Future epidemiologic studies seeking environmental risk factors for AD may benefit by making HC measurements on all subjects to decrease the variance associated with other potential risk factors

Ca2+ and synaptotagmin VII–dependent delivery of lysosomal membrane to nascent phagosomes

Synaptotagmin (Syt) VII is a ubiquitously expressed member of the Syt family of Ca2+ sensors. It is present on lysosomes in several cell types, where it regulates Ca2+-dependent exocytosis. Because [Ca2+]i and exocytosis have been associated with phagocytosis, we investigated the phagocytic ability of macrophages from Syt VII−/− mice. Syt VII−/− macrophages phagocytose normally at low particle/cell ratios but show a progressive inhibition in particle uptake under high load conditions. Complementation with Syt VII rescues this phenotype, but only when functional Ca2+-binding sites are retained. Reinforcing a role for Syt VII in Ca2+-dependent phagocytosis, particle uptake in Syt VII−/− macrophages is significantly less dependent on [Ca2+]i. Syt VII is concentrated on peripheral domains of lysosomal compartments, from where it is recruited to nascent phagosomes. Syt VII recruitment is rapidly followed by the delivery of Lamp1 to phagosomes, a process that is inhibited in Syt VII−/− macrophages. Thus, Syt VII regulates the Ca2+-dependent mobilization of lysosomes as a supplemental source of membrane during phagocytosis

On SIC-POVMs in Prime Dimensions

The generalized Pauli group and its normalizer, the Clifford group, have a rich mathematical structure which is relevant to the problem of constructing symmetric informationally complete POVMs (SIC-POVMs). To date, almost every known SIC-POVM fiducial vector is an eigenstate of a "canonical" unitary in the Clifford group. I show that every canonical unitary in prime dimensions p > 3 lies in the same conjugacy class of the Clifford group and give a class representative for all such dimensions. It follows that if even one such SIC-POVM fiducial vector is an eigenvector of such a unitary, then all of them are (for a given such dimension). I also conjecture that in all dimensions d, the number of conjugacy classes is bounded above by 3 and depends only on d mod 9, and I support this claim with computer computations in all dimensions < 48.Comment: 6 pages, no figures. v3 Refs added, improved discussion of previous work. Ref to a proof of the main conjecture also adde

Explaining global surface aerosol number concentrations in terms of primary emissions and particle formation

We use observations of total particle number concentration at 36 worldwide sites and a global aerosol model to quantify the primary and secondary sources of particle number. We show that emissions of primary particles can reasonably reproduce the spatial pattern of observed condensation nuclei (CN) (R2=0.51) but fail to explain the observed seasonal cycle at many sites (R2=0.1). The modeled CN concentration in the free troposphere is biased low (normalised mean bias, NMB=&#8722;88%) unless a secondary source of particles is included, for example from binary homogeneous nucleation of sulfuric acid and water (NMB=&#8722;25%). Simulated CN concentrations in the continental boundary layer (BL) are also biased low (NMB=&#8722;74%) unless the number emission of anthropogenic primary particles is increased or an empirical BL particle formation mechanism based on sulfuric acid is used. We find that the seasonal CN cycle observed at continental BL sites is better simulated by including a BL particle formation mechanism (R2=0.3) than by increasing the number emission from primary anthropogenic sources (R2=0.18). Using sensitivity tests we derive optimum rate coefficients for this nucleation mechanism, which agree with values derived from detailed case studies at individual sites

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription

Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV

American Cancer Society guidelines for breast cancer screening: update 2003

In 2003, the American Cancer Society updated its guidelines for early detection of breast cancer based on recommendations from a formal review of evidence and a recent workshop. The new screening recommendations address screening mammography, physical examination, screening older women and women with comorbid conditions, screening women at high risk, and new screening technologies