Inositol phosphatase SHIP1 is a primary target of miR-155

MicroRNA-155 (miR-155) has emerged as a critical regulator of immune cell development, function, and disease. However, the mechanistic basis for its impact on the hematopoietic system remains largely unresolved. Because miRNAs function by repressing specific mRNAs through direct 3′UTR interactions, we have searched for targets of miR-155 implicated in the regulation of hematopoiesis. In the present study, we identify Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1) as a direct target of miR-155, and, using gain and loss of function approaches, show that miR-155 represses SHIP1 through direct 3′UTR interactions that have been highly conserved throughout evolution. Repression of endogenous SHIP1 by miR-155 occurred following sustained over-expression of miR-155 in hematopoietic cells both in vitro and in vivo, and resulted in increased activation of the kinase Akt during the cellular response to LPS. Furthermore, SHIP1 was also repressed by physiologically regulated miR-155, which was observed in LPS-treated WT versus miR-155−/− primary macrophages. In mice, specific knockdown of SHIP1 in the hematopoietic system following retroviral delivery of a miR-155-formatted siRNA against SHIP1 resulted in a myeloproliferative disorder, with striking similarities to that observed in miR-155-expressing mice. Our study unveils a molecular link between miR-155 and SHIP1 and provides evidence that repression of SHIP1 is an important component of miR-155 biology

What is still limiting the deployment of cellulosic ethanol? Analysis of the current status of the sector

Ethanol production from cellulosic material is considered one of the most promising options for future biofuel production contributing to both the energy diversification and decarbonization of the transport sector, especially where electricity is not a viable option (e.g., aviation). Compared to conventional (or first generation) ethanol production from food and feed crops (mainly sugar and starch based crops), cellulosic (or second generation) ethanol provides better performance in terms of greenhouse gas (GHG) emissions savings and low risk of direct and indirect land-use change. However, despite the policy support (in terms of targets) and significant R&D funding in the last decade (both in EU and outside the EU), cellulosic ethanol production appears to be still limited. The paper provides a comprehensive overview of the status of cellulosic ethanol production in EU and outside EU, reviewing available literature and highlighting technical and non-technical barriers that still limit its production at commercial scale. The review shows that the cellulosic ethanol sector appears to be still stagnating, characterized by technical difficulties as well as high production costs. Competitiveness issues, against standard starch based ethanol, are evident considering many commercial scale cellulosic ethanol plants appear to be currently in idle or on-hold states

New results in rho^0 meson physics

We compare the predictions of a range of existing models based on the Vector Meson Dominance hypothesis with data on e^+ e^- -> pi^+ pi^$ and e^+ e^- -> mu^+ mu^- cross-sections and the phase and near-threshold behavior of the timelike pion form factor, with the aim of determining which (if any) of these models is capable of providing an accurate representation of the full range of experimental data. We find that, of the models considered, only that proposed by Bando et al. is able to consistently account for all information, provided one allows its parameter "a" to vary from the usual value of 2 to 2.4. Our fit with this model gives a point-like coupling (gamma pi^+ \pi^-) of magnitude ~ -e/6, while the common formulation of VMD excludes such a term. The resulting values for the rho mass and pi^+ pi^- and e^+e^- partial widths as well as the branching ratio for the decay omega -> pi^+ pi^- obtained within the context of this model are consistent with previous results.Comment: 34 pages with 7 figures. Published version also available at http://link.springer.de/link/service/journals/10052/tocs/t8002002.ht

Cleavage of dsRNAs hyper-edited by ADARs occurs at preferred editing sites

Long double-stranded RNAs (dsRNAs) may undergo covalent modification (hyper-editing) by adenosine deaminases that act on RNA (ADARs), whereby up to 50–60% of adenosine residues are converted to inosine. Previously, we have described a ribonuclease activity in various cell extracts that specifically targets dsRNAs hyper-edited by ADARs. Such a ribonuclease may play an important role in viral defense, or may alternatively be involved in down-regulation of other RNA duplexes. Cleavage of hyper-edited dsRNA occurs within sequences containing multiple IU pairs but not in duplexes that contain either isosteric GU pairs or Watson–Crick base pairs. Here, we describe experiments aimed at further characterizing cleavage of hyper-edited dsRNA. Using various inosine-containing dsRNAs we show that cleavage occurs preferentially at a site containing both IU and UI pairs, and that inclusion of even a single GU pair inhibits cleavage. We also show that cleavage occurs on both strands within a single dsRNA molecule and requires a 2′-OH group. Strikingly, we show that ADAR1, ADAR2 or dADAR all preferentially generate the preferred cleavage site when hyper-editing a long dsRNA

Laplace transform of spherical Bessel functions

We provide a simple analytic formula in terms of elementary functions for the Laplace transform j_{l}(p) of the spherical Bessel function than that appearing in the literature, and we show that any such integral transform is a polynomial of order l in the variable p with constant coefficients for the first l-1 powers, and with an inverse tangent function of argument 1/p as the coefficient of the power l. We apply this formula for the Laplace transform of the memory function related to the Langevin equation in a one-dimensional Debye model.Comment: 5 pages LATEX, no figures. Accepted 2002, Physica Script

The varying role of the GP in the pathway between colonoscopy and surgery for colorectal cancer: a retrospective cohort study

Extent: 11p.Objectives: To describe general practitioner (GP) involvement in the treatment referral pathway for colorectal cancer (CRC) patients. Design: A retrospective cohort analysis of linked data. Setting: A population-based sample of CRC patients diagnosed from August 2004 to December 2007 in New South Wales, Australia, using the 45 and Up Study, cancer registry diagnosis records, inpatient hospital records and Medicare claims records. Participants: 407 CRC patients who had a colonoscopy followed by surgery. Primary outcome measures: Patterns of GP consultations between colonoscopy and surgery (ie, between diagnosis and treatment). We investigated whether consulting a GP presurgery was associated with time to surgery, postsurgical GP consultations or rectal cancer cases having surgery in a centre with radiotherapy facilities. Results: Of the 407 patients, 43% (n=175) had at least one GP consultation between colonoscopy and surgery. The median time from colonoscopy to surgery was 27 days for those with an intervening GP consultation and 15 days for those without the consultation. 55% (n=223) had a GP consultation up to 30 days postsurgery; it was more common in cases of patients who consulted a GP presurgery than for those who did not (65% and 47%, respectively, adjusted OR 2.71, 95% CI 1.50 to 4.89, p=0.001). Of the 142 rectal cancer cases, 23% (n=33) had their surgery in a centre with radiotherapy facilities, with no difference between those who did and did not consult a GP presurgery (21% and 25% respectively, adjusted OR 0.84, 95% CI 0.27 to 2.63, p=0.76). Conclusions: Consulting a GP between colonoscopy and surgery was associated with a longer interval between diagnosis and treatment, and with further GP consultations postsurgery, but for rectal cancer cases it was not associated with treatment in a centre with radiotherapy facilities. GPs might require a more defined and systematic approach to CRC management.David Goldsbury, Mark Harris, Shane Pascoe, Michael Barton, Ian Olver, Allan Spigelman, Justin Beilby, Craig Veitch, David Weller, Dianne L O'Connel

Preparing for a Pandemic: Spending Dynamics and Panic Buying during the COVID-19 First Wave

In times of heightened uncertainty, consumers face incentives to build up precautionary stocks of essential supplies. We study consumer spending dynamics during one such time, the first infection wave of the COVID-19 pandemic, using household scanner data covering fast-moving consumer goods in the United Kingdom. We document large increases in demand for storable products, such as food staples and household supplies, in the days before lockdown. Households in all socio-economic groups exhibit unusually high demand pre-lockdown, but there is a clear gradient, with the largest demand spikes for wealthier households. Although stories of people purchasing extreme amounts received a lot of attention, higher aggregate demand was mainly driven by more households than usual choosing to buy storable products, with only small increases in average quantities bought on a given trip. Temporary limits on the number of units per transaction, introduced following the demand spike, are therefore unlikely to lead to the avoidance of stock-outs

Improving the Coherence Time of Superconducting Coplanar Resonators

The quality factor and energy decay time of superconducting resonators have been measured as a function of material, geometry, and magnetic field. Once the dissipation of trapped magnetic vortices is minimized, we identify surface two-level states (TLS) as an important decay mechanism. A wide gap between the center conductor and the ground plane, as well as use of the superconductor Re instead of Al, are shown to decrease loss. We also demonstrate that classical measurements of resonator quality factor at low excitation power are consistent with single-photon decay time measured using qubit-resonator swap experiments.Comment: 3 pages, 4 figures for the main paper; total 5 pages, 6 figures including supplementary material. Submitted to Applied Physics Letter