Is Honesty the Best Policy? Examining the Effect of Product Safety Communication on Blame Attributions in Causal Chains

This paper extends research on attribution theory through three studies examining how the accuracy and explicitness of product safety information communicated to various entities within a causal chain influences blame attributions after an accident. Unlike prior research, we find consistent evidence that entities in the causal chain were able to limit blame attributions by communicating safety information that’s quality met or exceeded the quality of information available to that entity. Entities did not, however, benefit from providing more accurate information than what had been communicated to them by previous members of the causal chain. This insight suggests that the controllability of information communicated played an important role in the relationship between accurate communication and blame attributions. Our findings provide meaningful insight into steps that organizations can take to limit their potential for receiving blame following an accident, helping to bridge the gap between basic and applied research

Predicting post-translational lysine acetylation using support vector machines

Motivation: Lysine acetylation is a post-translational protein modification and a primary regulatory mechanism that controls many cell signaling processes. Lysine acetylation sites are recognized by acetyltransferases and deacetylases through sequence patterns (motifs). Recently, we used high-resolution mass spectrometry to identify 3600 lysine acetylation sites on 1750 human proteins covering most of the previously annotated sites and providing the most comprehensive acetylome so far. This dataset should provide an excellent source to train support vector machines (SVMs) allowing the high accuracy in silico prediction of acetylated lysine residues

NetworKIN: a resource for exploring cellular phosphorylation networks

Protein kinases control cellular responses by phosphorylating specific substrates. Recent proteome-wide mapping of protein phosphorylation sites by mass spectrometry has discovered thousands of in vivo sites. Systematically assigning all 518 human kinases to all these sites is a challenging problem. The NetworKIN database (http://networkin.info) integrates consensus substrate motifs with context modelling for improved prediction of cellular kinase–substrate relations. Based on the latest human phosphoproteome from the Phospho.ELM and PhosphoSite databases, the resource offers insight into phosphorylation-modulated interaction networks. Here, we describe how NetworKIN can be used for both global and targeted molecular studies. Via the web interface users can query the database of precomputed kinase–substrate relations or obtain predictions on novel phosphoproteins. The database currently contains a predicted phosphorylation network with 20 224 site-specific interactions involving 3978 phosphoproteins and 73 human kinases from 20 families.Genome Canada (through Ontario Genomics Institute)National Institutes of Health (U.S.) (U54-CA112967)National Institutes of Health (U.S.) (GM60594)European Community’s Human Potential Programme (BioSapiens Network of Excellence (contract number LSHG-CT-2003-503265))European Community’s Human Potential Programme (ADIT Integrated Project (contract number LSHB-CT-2005511065)

Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients

<br>Background:Prostate cancer cell growth is dependent upon androgen receptor (AR) activation, which is regulated by specific kinases. The aim of the current study is to establish if AR phosphorylation by Cdk1 or ERK1/2 is of prognostic significance.</br> <br>Methods: Scansite 2.0 was utilised to predict which AR sites are phosphorylated by Cdk1 and ERK1/2. Immunohistochemistry for these sites was then performed on 90 hormone-naive prostate cancer specimens. The interaction between Cdk1/ERK1/2 and AR phosphorylation was investigated in vitro using LNCaP cells.</br><br>Results:Phosphorylation of AR at serine 515 (pAR(S515)) and PSA at diagnosis were independently associated with decreased time to biochemical relapse. Cdk1 and pCdk1(161), but not ERK1/2, correlated with pAR(S515). High expression of pAR(S515) in patients with a PSA at diagnosis of ≤20 ng ml(-1) was associated with shorter time to biochemical relapse (P=0.019). This translated into a reduction in disease-specific survival (10-year survival, 38.1% vs 100%, P<0.001). In vitro studies demonstrated that treatment with Roscovitine (a Cdk inhibitor) caused a reduction in pCdk1(161) expression, pAR(S515)expression and cellular proliferation.</br> <br>Conclusion: In prostate cancer patients with PSA at diagnosis of ≤20 ng ml(-1), phosphorylation of AR at serine 515 by Cdk1 may be an independent prognostic marker.</br&gt

Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells

The insulin/IGF-1 (insulin-like growth factor 1)-activated protein kinase Akt (also known as protein kinase B) phosphorylates Ser(487) in the ‘ST loop’ (serine/threonine-rich loop) within the C-terminal domain of AMPK-α1 (AMP-activated protein kinase-α1), leading to inhibition of phosphorylation by upstream kinases at the activating site, Thr(172). Surprisingly, the equivalent site on AMPK-α2, Ser(491), is not an Akt target and is modified instead by autophosphorylation. Stimulation of HEK (human embryonic kidney)-293 cells with IGF-1 caused reduced subsequent Thr(172) phosphorylation and activation of AMPK-α1 in response to the activator A769662 and the Ca(2+) ionophore A23187, effects we show to be dependent on Akt activation and Ser(487) phosphorylation. Consistent with this, in three PTEN (phosphatase and tensin homologue deleted on chromosome 10)-null tumour cell lines (in which the lipid phosphatase PTEN that normally restrains the Akt pathway is absent and Akt is thus hyperactivated), AMPK was resistant to activation by A769662. However, full AMPK activation could be restored by pharmacological inhibition of Akt, or by re-expression of active PTEN. We also show that inhibition of Thr(172) phosphorylation is due to interaction of the phosphorylated ST loop with basic side chains within the αC-helix of the kinase domain. Our findings reveal that a previously unrecognized effect of hyperactivation of Akt in tumour cells is to restrain activation of the LKB1 (liver kinase B1)–AMPK pathway, which would otherwise inhibit cell growth and proliferation

Klasifikacija dojki prema gustoći izborom značajki

Mammography as an x-ray method usually gives good results for lower density breasts while higher breast tissue densities significantly reduce the overall detection sensitivity and can lead to false negative results. In automatic detection algorithms knowledge about breast density can be useful for setting an appropriate decision threshold in order to produce more accurate detection. Because the overall intensity of mammograms is not directly correlated with the breast density we have decided to observe breast density as a texture classification problem. In this paper we propose breast density classification using feature selection process for different classifiers based on grayscale features of first and second order. In feature selection process different selection methods were used and obtained results show the improvement on overall classification by choosing the appropriate method and classifier. The classification accuracy has been tested on the mini-MIAS database and KBD-FER digital mammography database with different number of categories for each database. Obtained accuracy stretches between 97.2 % and 76.4 % for different number of categories.Mamografija je rendgenska metoda koja daje dobre rezultate pri slikanju dojki koje imaju manju gustoću, dok joj osjetljivost značajno opada pri snimanju dojki veće gustoće i time može doći do lažno pozitivnih rezultata. Poznavanje gustoće dojke može biti korisno kod algoritama za automatsku detekciju zbog mogućnosti određivanja praga odluke na osnovi tog znanja. S obzirom na to da ukupni intenzitet pojedinog mamograma nije izravno povezan s gustoćom, odlučili smo se promatrati gustoću kao problem klasifikacije teksture. U ovom radu predlažemo klasifikaciju dojki prema gustoći izborom izdvojenih značajki intenziteta prvog i drugog reda za različite klasifikatore. Za određivanje prikladnih značajki koristili smo različite metode i tako dobivene značajke pokazale su bolju točnost klasifikacije za odabrane klasifikatore. Točnost klasifikacije testirali smo na bazi mamografskih slika mini-MIAS i bazi digitalnih mamografskih slika KBD-FER s različitim brojem kategorija u koje su slike bile podijeljene. Postignuta točnost klasifikacije proteže se između 97,2 % i 76,4 % za različit broj kategorija u koje su mamogrami podijeljeni

PHOSIDA 2011: the posttranslational modification database

The primary purpose of PHOSIDA (http://www.phosida.com) is to manage posttranslational modification sites of various species ranging from bacteria to human. Since its last report, PHOSIDA has grown significantly in size and evolved in scope. It comprises more than 80 000 phosphorylated, N-glycosylated or acetylated sites from nine different species. All sites are obtained from high-resolution mass spectrometric data using the same stringent quality criteria. One of the main distinguishing features of PHOSIDA is the provision of a wide range of analysis tools. PHOSIDA is comprised of three main components: the database environment, the prediction platform and the toolkit section. The database environment integrates and combines high-resolution proteomic data with multiple annotations. High-accuracy species-specific phosphorylation and acetylation site predictors, trained on the modification sites contained in PHOSIDA, allow the in silico determination of modified sites on any protein on the basis of the primary sequence. The toolkit section contains methods that search for sequence motif matches or identify de novo consensus, sequences from large scale data sets

Influenza in Migratory Birds and Evidence of Limited Intercontinental Virus Exchange

Migratory waterfowl of the world are the natural reservoirs of influenza viruses of all known subtypes. However, it is unknown whether these waterfowl perpetuate highly pathogenic (HP) H5 and H7 avian influenza viruses. Here we report influenza virus surveillance from 2001 to 2006 in wild ducks in Alberta, Canada, and in shorebirds and gulls at Delaware Bay (New Jersey), United States, and examine the frequency of exchange of influenza viruses between the Eurasian and American virus clades, or superfamilies. Influenza viruses belonging to each of the subtypes H1 through H13 and N1 through N9 were detected in these waterfowl, but H14 and H15 were not found. Viruses of the HP Asian H5N1 subtypes were not detected, and serologic studies in adult mallard ducks provided no evidence of their circulation. The recently described H16 subtype of influenza viruses was detected in American shorebirds and gulls but not in ducks. We also found an unusual cluster of H7N3 influenza viruses in shorebirds and gulls that was able to replicate well in chickens and kill chicken embryos. Genetic analysis of 6,767 avian influenza gene segments and 248 complete avian influenza viruses supported the notion that the exchange of entire influenza viruses between the Eurasian and American clades does not occur frequently. Overall, the available evidence does not support the perpetuation of HP H5N1 influenza in migratory birds and suggests that the introduction of HP Asian H5N1 to the Americas by migratory birds is likely to be a rare event

Partitioning of Minimotifs Based on Function with Improved Prediction Accuracy

Background: Minimotifs are short contiguous peptide sequences in proteins that are known to have a function in at least one other protein. One of the principal limitations in minimotif prediction is that false positives limit the usefulness of this approach. As a step toward resolving this problem we have built, implemented, and tested a new data-driven algorithm that reduces false-positive predictions. Methodology/Principal Findings: Certain domains and minimotifs are known to be strongly associated with a known cellular process or molecular function. Therefore, we hypothesized that by restricting minimotif predictions to those where the minimotif containing protein and target protein have a related cellular or molecular function, the prediction is more likely to be accurate. This filter was implemented in Minimotif Miner using function annotations from the Gene Ontology. We have also combined two filters that are based on entirely different principles and this combined filter has a better predictability than the individual components. Conclusions/Significance: Testing these functional filters on known and random minimotifs has revealed that they are capable of separating true motifs from false positives. In particular, for the cellular function filter, the percentage of known minimotifs that are not removed by the filter is,4.6 times that of random minimotifs. For the molecular function filter this ratio is,2.9. These results, together with the comparison with the published frequency score filter, strongly suggest tha

Invasions by Eurasian Avian Influenza Virus H6 Genes and Replacement of Its North American Clade

This study showed frequent cross-hemisphere virus movement, which can affect the risk posed to poultry and humans