Gamma oscillatory amplitude encodes stimulus intensity in primary somatosensory cortex

Gamma oscillations have previously been linked to pain perception and it has been hypothesised that they may have a potential role in encoding pain intensity. Stimulus response experiments have reported an increase in activity in the primary somatosensory cortex (SI) with increasing stimulus intensity, but the specific role of oscillatory dynamics in this change in activation remains unclear. In this study, Magnetoencephalography (MEG) was used to investigate the changes in cortical oscillations during 4 different intensities of a train of electrical stimuli to the right index finger, ranging from low sensation to strong pain. In those participants showing changes in evoked oscillatory gamma in SI during stimulation, the strength of the gamma power was found to increase with increasing stimulus intensity at both pain and sub-pain thresholds. These results suggest that evoked gamma oscillations in SI are not specific to pain but may have a role in encoding somatosensory stimulus intensity. © 2013 Rossiter, Worthen, Witton, Hall and Furlong

Upconversion nanoparticles for sensing pH.

Upconversion nanoparticles (UCNPs) can provide a vehicle for chemical imaging by coupling chemically sensitive dyes and quenchers. The mechanism for coupling of two anthraquinone dyes, Calcium Red and Alizarin Red S, was investigated as a function of pH. The green emission band of the UCNPs was quenched by a pH-dependent inner filter effect (IFE) while the red emission band remained unchanged and acted as the reference signal for ratiometric pH measurements. Contrary to previous expectation, there was little evidence for a resonance energy transfer (RET) mechanism even when the anthraquinones were attached onto the UCNPs through electrostatic attraction. Since the UCNPs are point emitters, only emitters close to the surface of the UCNP are within the expected Förster distance and UC-RET is <10%. The theoretical and experimental analysis of the interaction between UCNPs and pH-sensitive quenchers will allow the design of UCNP pH sensors for determination of pH via IFE.This work was supported by the EPSRC Cambridge NanoDTC, EP/L015978/

Coloron Phenomenology

A flavor-universal extension of the strong interactions was recently proposed in response to the apparent excess of high-$E_T$ jets in the inclusive jet spectrum measured at the Tevatron. This paper studies the color octet of massive gauge bosons (`colorons') that is present in the low-energy spectrum of the model's Higgs phase. Constraints from searches for new particles decaying to dijets and from measurements of the weak-interaction $\rho$ parameter imply that the colorons must have masses greater than 870-1000 GeV. The implications of recent Tevatron data and the prospective input from future experiments are also discussed.Comment: 13 pages, 4 embedded Postscript figures, LaTeX, full postscript version also available at http://smyrd.bu.edu/htfigs/htfigs.html rectified confusing phrase at end of sub-section on 'dijets

Comparative Study of Multicellular Tumor Spheroid Formation Methods and Implications for Drug Screening

Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Multicellular tumor spheroids (MCTS) are a popular method for three-dimensional (3D) cell culture, because they capture some aspects of the dimensionality, cell–cell contact, and cell–matrix interactions seen in vivo. Many approaches exist to create MCTS from cell lines, and they have been used to study tumor cell invasion, growth, and how cells respond to drugs in physiologically relevant 3D microenvironments. However, there are several discrepancies in the observations made of cell behaviors when comparing between MCTS formation methods. To resolve these inconsistencies, we created and compared the behavior of breast, prostate, and ovarian cancer cells across three MCTS formation methods: in polyNIPAAM gels, in microwells, or in suspension culture. These methods formed MCTS via proliferation from single cells or passive aggregation, and therefore showed differential reliance on genes important for cell–cell or cell–matrix interactions. We also found that the MCTS formation method dictated drug sensitivity, where MCTS formed over longer periods of time via clonal growth were more resistant to treatment. Toward clinical application, we compared an ovarian cancer cell line MCTS formed in polyNIPAAM with cells from patient-derived malignant ascites. The method that relied on clonal growth (PolyNIPAAM gel) was more time and cost intensive, but yielded MCTS that were uniformly spherical, and exhibited the most reproducible drug responses. Conversely, MCTS methods that relied on aggregation were faster, but yielded MCTS with grape-like, lobular structures. These three MCTS formation methods differed in culture time requirements and complexity, and had distinct drug response profiles, suggesting the choice of MCTS formation method should be carefully chosen based on the application required

Z→bbˉZ\to b\bar b in U(1)RU(1)_R Symmetric Supersymmetry

We compute the one-loop corrections to the $Z \to b\bar{b}$ vertex in the $U(1)_R$ symmetric minimal supersymmetric extension of the standard model. We find that the predicted value of $R_b$ is consistent with experiment if the mass of the lighter top squark is no more than 180 GeV. Furthermore, other data combines to place a lower bound of 88 GeV on the mass of the light top squark. A top squark in this mass range should be accessible to searches by experiments at FNAL and LEP.Comment: Corrected typos; added footnotes and a reference. 19 pages, LaTeX, includes 8 figures, full postscript version at http://smyrd.bu.edu/htfigs/htfigs.htm

Hubble Space Telescope Ultraviolet Spectroscopy of Fourteen Low-Redshift Quasars

We present low-resolution ultraviolet spectra of 14 low redshift (z<0.8) quasars observed with HST/STIS as part of a Snap project to understand the relationship between quasar outflows and luminosity. By design, all observations cover the CIV emission line. Nine of the quasars are from the Hamburg-ESO catalog, three are from the Palomar-Green catalog, and one is from the Parkes catalog. The sample contains a few interesting quasars including two broad absorption line (BAL) quasars (HE0143-3535, HE0436-2614), one quasar with a mini-BAL (HE1105-0746), and one quasar with associated narrow absorption (HE0409-5004). These BAL quasars are among the brightest known (though not the most luminous) since they lie at z<0.8. We compare the properties of these BAL quasars to the z1.4 Large Bright Quasar samples. By design, our objects sample luminosities in between these two surveys, and our four absorbed objects are consistent with the v ~ L^0.62 relation derived by Laor & Brandt (2002). Another quasar, HE0441-2826, contains extremely weak emission lines and our spectrum is consistent with a simple power-law continuum. The quasar is radio-loud, but has a steep spectral index and a lobe-dominated morphology, which argues against it being a blazar. The unusual spectrum of this quasar resembles the spectra of the quasars PG1407+265, SDSSJ1136+0242, and PKS1004+13 for which several possible explanations have been entertained.Comment: Uses aastex.cls, 21 pages in preprint mode, including 6 figures and 2 tables; accepted for publication in The Astronomical Journal (projected vol 133

Non-antibiotic pharmaceuticals are toxic against <i>Escherichia coli</i> with no evolution of cross-resistance to antibiotics

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent released by manufacturing facilities. In addition to antibiotics, pharmaceutical plants also produce non-antibiotic pharmaceuticals, both the active ingredients and other components of the formulations. The effect of these on the surrounding microbial communities is less clear. We aimed to assess whether non-antibiotic pharmaceuticals and other compounds produced by pharmaceutical plants have inherent toxicity, and whether long-term exposure might result in significant genetic changes or select for cross-resistance to antibiotics. To this end, we screened four non-antibiotic pharmaceuticals (acetaminophen, ibuprofen, propranolol, metformin) and titanium dioxide for toxicity against Escherichia coli K-12 MG1655 and conducted a 30 day selection experiment to assess the effect of long-term exposure. All compounds reduced the maximum optical density reached by E. coli at a range of concentrations including one of environmental relevance, with transcriptome analysis identifying upregulated genes related to stress response and multidrug efflux in response ibuprofen treatment. The compounds did not select for significant genetic changes following a 30 day exposure, and no evidence of selection for cross-resistance to antibiotics was observed for population evolved in the presence of ibuprofen in spite of the differential gene expression after exposure to this compound. This work suggests that these compounds, at environmental concentrations, do not select for cross-resistance to antibiotics in E. coli

De novo assembly of the cattle reference genome with single-molecule sequencing.

BackgroundMajor advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10-12 years. These tools depend upon the Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies.ResultsWe present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is &gt;250× more continuous than the original assembly, with contig N50 &gt;25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use.ConclusionsWe demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis

Reactive oxygen species (ROS) have an equivocal role in myocardial ischaemia reperfusion injury. Within the cardiomyocyte, mitochondria are both a major source and target of ROS. We evaluate the effects of a selective, dose-dependent increase in mitochondrial ROS levels on cardiac physiology using the mitochondria-targeted redox cycler MitoParaquat (MitoPQ). Low levels of ROS decrease the susceptibility of neonatal rat ventricular myocytes (NRVMs) to anoxia/reoxygenation injury and also cause profound protection in an in vivo mouse model of ischaemia/reperfusion. However higher doses of MitoPQ resulted in a progressive alteration of intracellular [Ca2+] homeostasis and mitochondrial function in vitro, leading to dysfunction and death at high doses. Our data show that a primary increase in mitochondrial ROS can alter cellular function, and support a hormetic model in which low levels of ROS are cardioprotective while higher levels of ROS are cardiotoxic.The work is supported by an MRC Studentship to JFM and a Wellcome Trust Investigator award to RCH (110158/Z/15/Z), the Leducq Transatlantic Network of Excellence, and the University of Padova Strategico grant (FDL). Part of the study was funded by an MRC Project Grant to TK (MR/P000320/1). Michele Cariello is thanked for help with cyclic voltammetry