Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA

Identification of sex hormone-binding globulin in the human hypothalamus

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

Maximization of propylene in an industrial FCC unit

YesThe FCC riser cracks gas oil into useful fuels such as gasoline, diesel and some lighter products such as ethylene and propylene, which are major building blocks for the polyethylene and polypropylene production. The production objective of the riser is usually the maximization of gasoline and diesel, but it can also be to maximize propylene. The optimization and parameter estimation of a six-lumped catalytic cracking reaction of gas oil in FCC is carried out to maximize the yield of propylene using an optimisation framework developed in gPROMS software 5.0 by optimizing mass flow rates and temperatures of catalyst and gas oil. The optimal values of 290.8 kg/s mass flow rate of catalyst and 53.4 kg/s mass flow rate of gas oil were obtained as propylene yield is maximized to give 8.95 wt%. When compared with the base case simulation value of 4.59 wt% propylene yield, the maximized propylene yield is increased by 95%

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

<b>Background</b>: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. <b>Methods/design</b>: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Atrial Fibrillation and Delayed Gastric Emptying

Background: Atrial fibrillation and delayed gastric emptying (DGE) are common after pancreaticoduodenectomy. Our aim was to investigate a potential relationship between atrial fibrillation and DGE, which we defined as failure to tolerate a regular diet by the 7 th postoperative day. Methods: We performed a retrospective chart review of 249 patients who underwent pancreaticoduodenectomy at our institution between 2000 and 2009. Data was analyzed with Fisher exact test for categorical variables and Mann-Whitney U or unpaired T-test for continuous variables. Results: Approximately 5 % of the 249 patients included in the analysis experienced at least one episode of postoperative atrial fibrillation. Median age of patients with atrial fibrillation was 74 years, compared with 66 years in patients without atrial fibrillation (p = 0.0005). Patients with atrial fibrillation were more likely to have a history of atrial fibrillation (p = 0.03). 92 % of the patients with atrial fibrillation suffered from DGE, compared to 46 % of patients without atrial fibrillation (p = 0.0007). This association held true when controlling for age. Conclusion: Patients with postoperative atrial fibrillation are more likely to experience delayed gastric emptying. Interventions to manage delayed gastric function might be prudent in patients at high risk for postoperative atrial fibrillation

General Analysis of Antideuteron Searches for Dark Matter

Low energy cosmic ray antideuterons provide a unique low background channel for indirect detection of dark matter. We compute the cosmic ray flux of antideuterons from hadronic annihilations of dark matter for various Standard Model final states and determine the mass reach of two future experiments (AMS-02 and GAPS) designed to greatly increase the sensitivity of antideuteron detection over current bounds. We consider generic models of scalar, fermion, and massive vector bosons as thermal dark matter, describe their basic features relevant to direct and indirect detection, and discuss the implications of direct detection bounds on models of dark matter as a thermal relic. We also consider specific dark matter candidates and assess their potential for detection via antideuterons from their hadronic annihilation channels. Since the dark matter mass reach of the GAPS experiment can be well above 100 GeV, we find that antideuterons can be a good indirect detection channel for a variety of thermal relic electroweak scale dark matter candidates, even when the rate for direct detection is highly suppressed.Comment: 44 pages, 15 Figure