Memory-encoding vibrations in a disconnecting air bubble

Many nonlinear processes, such as the propagation of waves over an ocean or the transmission of light pulses down an optical fibre1, are integrable in the sense that the dynamics has as many conserved quantities as there are independent variables. The result is a time evolution that retains a complete memory of the initial state. In contrast, the nonlinear dynamics near a finite-time singularity, in which physical quantities such as pressure or velocity diverge at a point in time, is believed to evolve towards a universal form, one independent of the initial state2. The break-up of a water drop in air3 or a viscous liquid inside an immiscible oil4,5 are processes that conform to this second scenario. These opposing scenarios collide in the nonlinearity produced by the formation of a finite-time singularity that is also integrable. We demonstrate here that the result is a novel dynamics with a dual character

Molecular characterization and antiviral activity test of common drugs against echovirus 18 isolated in Korea

Genetic diversity and antiviral activity for five common antiviral drugs of echovirus (ECV) 5 isolated in Korea have been described. The present study extended these tests to a Korean ECV 18 isolate. An outbreak of aseptic meningitis caused by the ECV 18 isolate was reported in Korea in 2005, marking the first time this virus had been identified in the country since enterovirus surveillance began in 1993. Using a sample isolated from stool specimen of a 5-year-old male patient with aseptic meningitis, the complete genome sequence was obtained and was compared it with the Metcalf prototype strain. Unlike the ECV5 isolate, the 3' untranslated region had the highest identity value (94.2%) at the nucleotide level, while, at the amino acid level, the P2 region displayed the highest identity value (96.9%). These two strains shared all cleavage sites, with the exception of the 2B/2C site, which was RQ/NN in the Metcalf strain but RQ/NS in the Korean ECV 18 isolate. In Vero cells infected with the Korean ECV 18 isolate, no cytotoxicity was observed in the presence of azidothymidine, acyclovir, amantadine, lamivudine, or ribavirin, when the drugs were administered at a CC50 value >100 μg/mL. Of the five drugs, only amantadine (IC50: 4.97 ± 0.77 μg/mL, TI: 20.12) and ribavirin (IC50: 7.63 ± 0.87 μg/mL, TI: 13.11) had any antiviral activity against the Korean ECV 18 isolate in the five antiviral drugs. These antiviral activity effects were similar with results of the Korean ECV5 isolate

Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis

Background Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Methods Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. Results The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. Conclusions For the first time this data associates altered CDK5 substrate phosphorylation with oncogenesis in some but not all tumour types, implicating altered CDK5 activity in aspects of pathogenesis. These data identify a novel oncogenic mechanism where CDK5 activation induces CRMP2A phosphorylation in the nuclei of tumour cells

Color perception deficits in co-existing attention-deficit/hyperactivity disorder and chronic tic disorders

Preliminary findings suggest that color perception, particularly of blue-yellow stimuli, is impaired in attention-deficit/hyperactivity disorder (ADHD) as well as in chronic tic disorders (CTD). However, these findings have been not replicated and it is unclear what these deficits mean for the comorbidity of ADHD + CTD. Four groups (ADHD, CTD, ADHD + CTD, controls) of children with similar age, IQ and gender distribution were investigated with the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Color-Word Task using a factorial design. Color perception deficits, as indexed by the FMT, were found for both main factors (ADHD and CTD), but there were no interaction effects. A preponderance of deficits on the blue-yellow compared to the red-green axis was detected for ADHD. In the Stroop task only the 'pure' ADHD group showed impairments in interference control and other parameters of Stroop performance. No significant correlations between any FMT parameter and color naming in the Stroop task were found. Basic color perception deficits in both ADHD and CTD could be found. Beyond that, it could be shown that these deficits are additive in the case of comorbidity (ADHD + CTD). Performance deficits on the Stroop task were present only in the 'pure' ADHD group. Hence, the latter may be compensated in the comorbid group by good prefrontal capabilities of CTD. The influence of color perception deficits on Stroop task performance might be negligible. © 2007 Springer-Verlag

Kidney transplant in diabetic patients: modalities, indications and results

<p>Abstract</p> <p>Background</p> <p>Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy.</p> <p>Conclusion</p> <p>Type 1 and 2 diabetic patients present higher survival rates after transplant in comparison to the dialysis therapy, although the prevalence of cardiovascular events and infectious complications remain higher than in the general population.</p

CD14 Signaling Restrains Chronic Inflammation through Induction of p38-MAPK/SOCS-Dependent Tolerance

Current thinking emphasizes the primacy of CD14 in facilitating recognition of microbes by certain TLRs to initiate pro-inflammatory signaling events and the importance of p38-MAPK in augmenting such responses. Herein, this paradigm is challenged by demonstrating that recognition of live Borrelia burgdorferi not only triggers an inflammatory response in the absence of CD14, but one that is, in part, a consequence of altered PI3K/AKT/p38-MAPK signaling and impaired negative regulation of TLR2. CD14 deficiency results in increased localization of PI3K to lipid rafts, hyperphosphorylation of AKT, and reduced activation of p38. Such aberrant signaling leads to decreased negative regulation by SOCS1, SOCS3, and CIS, thereby compromising the induction of tolerance in macrophages and engendering more severe and persistent inflammatory responses to B. burgdorferi. Importantly, these altered signaling events and the higher cytokine production observed can be mimicked through shRNA and pharmacological inhibition of p38 activity in CD14-expressing macrophages. Perturbation of this CD14/p38-MAPK-dependent immune regulation may underlie development of infectious chronic inflammatory syndromes

BosR (BB0647) Controls the RpoN-RpoS Regulatory Pathway and Virulence Expression in Borrelia burgdorferi by a Novel DNA-Binding Mechanism

In Borrelia burgdorferi (Bb), the Lyme disease spirochete, the alternative σ factor σ54 (RpoN) directly activates transcription of another alternative σ factor, σS (RpoS) which, in turn, controls the expression of virulence-associated membrane lipoproteins. As is customary in σ54-dependent gene control, a putative NtrC-like enhancer-binding protein, Rrp2, is required to activate the RpoN-RpoS pathway. However, recently it was found that rpoS transcription in Bb also requires another regulator, BosR, which was previously designated as a Fur or PerR homolog. Given this unexpected requirement for a second activator to promote σ54-dependent gene transcription, and the fact that regulatory mechanisms among similar species of pathogenic bacteria can be strain-specific, we sought to confirm the regulatory role of BosR in a second virulent strain (strain 297) of Bb. Indeed, BosR displayed the same influence over lipoprotein expression and mammalian infectivity for strain Bb 297 that were previously noted for Bb strain B31. We subsequently found that recombinant BosR (rBosR) bound to the rpoS gene at three distinct sites, and that binding occurred despite the absence of consensus Fur or Per boxes. This led to the identification of a novel direct repeat sequence (TAAATTAAAT) critical for rBosR binding in vitro. Mutations in the repeat sequence markedly inhibited or abolished rBosR binding. Taken together, our studies provide new mechanistic insights into how BosR likely acts directly on rpoS as a positive transcriptional activator. Additional novelty is engendered by the facts that, although BosR is a Fur or PerR homolog and it contains zinc (like Fur and PerR), it has other unique features that clearly set it apart from these other regulators. Our findings also have broader implications regarding a previously unappreciated layer of control that can be involved in σ54–dependent gene regulation in bacteria

Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant

Farmers’ perceptions of climate change : identifying types

Ambitious targets to reduce greenhouse gas (GHG) emissions from agriculture have been set by both national governments and their respective livestock sectors. We hypothesize that farmer self-identity influences their assessment of climate change and their willingness to im- plement measures which address the issue. Perceptions of climate change were determined from 286 beef/sheep farmers and evaluated using principal component analysis (PCA). The analysis elicits two components which evaluate identity (productivism and environmental responsibility), and two components which evaluate behavioral capacity to adopt mitigation and adaptation measures (awareness and risk perception). Subsequent Cluster Analyses reveal four farmer types based on the PCA scores. ‘The Productivist’ and ‘The Countryside Steward’ portray low levels of awareness of climate change, but differ in their motivation to adopt pro-environmental behavior. Conversely, both ‘The Environmentalist’ and ‘The Dejected’ score higher in their awareness of the issue. In addition, ‘The Dejected’ holds a high sense of perceived risk; however, their awareness is not conflated with an explicit understanding of agricultural GHG sources. With the exception of ‘The Environmentalist’, there is an evident disconnect between perceptions of agricultural emission sources and their contribution towards GHG emissions amongst all types. If such linkages are not con- ceptualized, it is unlikely that behavioral capacities will be realized. Effective communication channels which encour- age action should target farmers based on the groupings depicted. Therefore, understanding farmer types through the constructs used in this study can facilitate effective and tai- lored policy development and implementation

Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-β

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-β and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-α, IL-6, IL-10 and IL-1β in monocytes than did lysates. Secreted IL-18, which, like IL-1β, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine production by TLR2-deficient murine macrophages was only moderately diminished in response to live Bb but was drastically impaired against lysates; TLR2 deficiency had no significant effect on uptake and degradation of spirochetes. As with PBMCs, live Bb was a much more potent inducer of IFN-β and ISGs in isolated monocytes than were lysates or a synthetic TLR2 agonist. Collectively, our results indicate that the enhanced innate immune responses of monocytes following phagocytosis of live Bb have both TLR2-dependent and -independent components and that the latter induce transcription of type I IFNs and ISGs