Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

A hysteretic multiscale formulation for nonlinear dynamic analysis of composite materials

This article has been made available through the Brunel Open Access Publishing Fund.A new multiscale finite element formulation is presented for nonlinear dynamic analysis of heterogeneous structures. The proposed multiscale approach utilizes the hysteretic finite element method to model the microstructure. Using the proposed computational scheme, the micro-basis functions, that are used to map the microdisplacement components to the coarse mesh, are only evaluated once and remain constant throughout the analysis procedure. This is accomplished by treating inelasticity at the micro-elemental level through properly defined hysteretic evolution equations. Two types of imposed boundary conditions are considered for the derivation of the multiscale basis functions, namely the linear and periodic boundary conditions. The validity of the proposed formulation as well as its computational efficiency are verified through illustrative numerical experiments

Observation of contemporaneous optical radiation from a gamma-ray burst

The origin of gamma-ray bursts (GRBs) has been enigmatic since their discovery. The situation improved dramatically in 1997, when the rapid availability of precise coordinates for the bursts allowed the detection of faint optical and radio afterglows - optical spectra thus obtained have demonstrated conclusively that the bursts occur at cosmological distances. But, despite efforts by several groups, optical detection has not hitherto been achieved during the brief duration of a burst. Here we report the detection of bright optical emission from GRB990123 while the burst was still in progress. Our observations begin 22 seconds after the onset of the burst and show an increase in brightness by a factor of 14 during the first 25 seconds; the brightness then declines by a factor of 100, at which point (700 seconds after the burst onset) it falls below our detection threshold. The redshift of this burst, approximately 1.6, implies a peak optical luminosity of 5 times 10^{49} erg per second. Optical emission from gamma-ray bursts has been generally thought to take place at the shock fronts generated by interaction of the primary energy source with the surrounding medium, where the gamma-rays might also be produced. The lack of a significant change in the gamma-ray light curve when the optical emission develops suggests that the gamma-rays are not produced at the shock front, but closer to the site of the original explosion.Comment: 10 pages, 2 figures. Accepted for publication in Nature. For additional information see http://www.umich.edu/~rotse

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

A new technique for measuring fistula flow using venous blood gas oxygen saturation in patients with a central venous catheter

Background. Doppler ultrasound (DU) monitoring early after arteriovenous fistula (AVF) creation allows the identification of low blood flow (Qa) requiring prompt revision, but it is costly (needs skilled operators and technical instruments) and is not available in all dialysis units. Therefore alternative first-line methods to measure Qa would be welcomed.We reasoned that once an AVF is created, an increment in central venous oxygen saturation (ScvO2) is predictable and proportional to Qa. Methods. Accordingly, in patients receiving dialysis through a central venous catheter (CVC) in whom an AVF was created, we measured, by means of blood gas analysis, the ScvO2 increment before and after manual compression of the arteriovenous shunt and verified its correlation with DU-measured Qa. Results. We sampled blood gas in 18 patients with CVC and AVF before and after 30 s manual compression of the AVF. ScvO2 averaged 70.563% before and 65.263% after AVF closure, with an average drop of 5.163% (range 1–12). AVF Qa, which was measured within 24h by means of DU, averaged 6356349 mL/min (range 50–1300) and was strictly and positively correlated with DScvO2 (r ¼ 0.954, P<0.0001). Conclusions. Therefore we suggest that in patients with CVC and a newly created AVF, it is possible to monitor AVF Qa without DU by simply measuring blood gas and DScvO2. This technique is simple, cheap, repeatable, non-invasive and operator independent and represents a new useful screening test to detect delayed AVF access maturation deserving prompt DU measurement and surgical revision. It helps to quickly identify patients in urgent need of DU verification and possible surgical revision. Regrettably, it is applicable only in patients with CVC

Draft genome sequence of the naphthalene degrader Herbaspirillum sp. strain RV1423

Herbaspirillum sp. strain RV1423 was isolated from a site contaminated with alkanes and aromatic compounds and harbors the complete pathway for naphthalene degradation. The new features found in RV1423 increase considerably the versatility and the catabolic potential of a genus of bacteria previously considered mainly to be diazotrophic endophytes to plants

False Elevation of Volume Determined by Bladder Scanner Secondary to Bowel Obstruction

Bladder scanners allow for quick determination of bladder volumes (BV) with minimal training. BV measured by a machine is generally accurate; however, circumstances exist in which falsely elevated BVs are reported. This case details a patient with a significant small bowel obstruction (SBO) due to superior mesenteric artery syndrome causing a falsely elevated BV. We believe this is the first case report of a SBO causing an elevated BV by bladder scanner. Emergency physicians should be aware of the pitfalls of using bladder scanners, and use their point-of-care ultrasound skills when possible to expand their differential

Use of the intraosseous screw for unilateral upper molar distalization and found well balanced occlusion

BACKGROUND: The aim of this study was to present a temporary anchorage device with intraosseous screw for unilateral molar distalization to make a space for the impacted premolar and to found well balanced occlusion in a case. CASE PRESENTATION: A 13-year-old male who have an impacted premolar is presented with skeletal Class I and dental Class 2 relationship. The screw was placed and immediately loaded to distalize the left upper first and second molar. The average distalization time to achieve an overcorrected Class I molar relationship was 3.6 months. There was no change in overjet, overbite, or mandibular plane angle measurements. Mild protrusion (0.5 mm) of the upper left central incisor was also recorded. CONCLUSION: Immediately loaded intraosseous screw-supported anchorage unit was successful in achieving sufficient unilateral molar distalization without anchorage loss. This treatment procedure was an alternative treatment to the extraction therapy