IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR initiating a mesenchymal program in stromal, epithelial, and cancer cells

IL11 initiates fibroblast activation but also causes epithelial cell dysfunction. The mechanisms underlying these processes are not known. We report that IL11-stimulated ERK/P90RSK activity causes the phosphorylation of LKB1 at S325 and S428, leading to its inactivation. This inhibits AMPK and activates mTOR across cell types. In stromal cells, IL11-stimulated ERK activity inhibits LKB1/AMPK which is associated with mTOR activation, ⍺SMA expression, and myofibroblast transformation. In hepatocytes and epithelial cells, IL11/ERK activity inhibits LKB1/AMPK leading to mTOR activation, SNAI1 expression, and cell dysfunction. Across cells, IL11-induced phenotypes were inhibited by metformin stimulated AMPK activation. In mice, genetic or pharmacologic manipulation of IL11 activity revealed a critical role of IL11/ERK signaling for LKB1/AMPK inhibition and mTOR activation in fatty liver disease. These data identify the IL11/mTOR axis as a signaling commonality in stromal, epithelial, and cancer cells and reveal a shared IL11-driven mesenchymal program across cell types

Molecular lens applied to benzene and carbon disulfide molecular beams

A molecular lens of the nonresonant dipole force formed by focusing a nanosecond IR laser pulse has been applied to benzene and CS2 molecular beams. Using the velocity map imaging technique for molecular ray tracing, characteristic molecular lens parameters including the focal length (f ), minimum beam width (W), and distance to the minimum beam width position (D) were determined. The laser intensity dependence of the observed lens parameters was in good agreement with theoretical predictions. W was independent of the laser peak intensity (I-0), whereas f and D varied linearly with 1/I-0. The differences in lens parameters between the molecular species were well correlated with the polarizability per mass values of the molecules. A high chromatographic resolution of Rs = 0.84 was achieved between the images of benzene molecular beams undeflected and deflected by the lens. The possibilities for a new type of chromatography are discussed.open293

ISO LWS observations of planetary nebula fine-structure lines

We have obtained 43–198 μm far-infrared (IR) spectra for a sample of 51 Galactic planetary nebulae (PN) and protoplanetary nebulae (PPN), using the Long Wavelength Spectrometer (LWS) on board the Infrared Space Observatory (ISO). Spectra were also obtained of the former PN candidate Lo 14. The spectra yield fluxes for the fine-structure lines [N II] 122 μm, [N III] 57 μm and [O III] 52 and 88 μm emitted in the ionized regions and the [O I] 63- and 146-μm and [C II] 158-μm lines from the photodissociation regions (PDRs), which have been used to determine electron densities and ionic abundances for the ionized regions and densities, temperatures and gas masses for the PDRs. The strong [N III] and [O III] emission lines detected in the LWS spectrum taken centred on Lo 14 could be associated with the nearby strong radio and infrared source G 331.5–0.1. We find that the electron densities yielded by the [O III] 88 μm/52 μm doublet ratio are systematically lower than those derived from the optical [Ar IV] λ4740/λ4711 and [Cl III] λ5537/λ5517 doublet ratios, which have much higher critical densities than the 52- and 88-μm lines, suggesting the presence of density inhomogeneities in the nebulae. Ionic abundances, N+/H+,N2+/H+ and O2+/H+, as well as the N2+/O2+ abundance ratio, which provides a good approximation to the N/O elemental abundance ratio, are derived. Although ionic abundances relative to H+ deduced from the far-IR fine-structure lines are sensitive to the adopted electron density and the presence of density inhomogeneities, the strong dependence on the nebular physical conditions is largely cancelled out when N2+/O2+ is calculated from the 57 μm/(52 μm+88 μm) flux ratio, owing to the similarity of the critical densities of the lines involved. The temperatures and densities of the PDRs around 24 PN have been determined from the observed [O I] and [C II] line intensity ratios. Except for a few objects, the deduced temperatures fall between 200 and 500 K, peaking around 250 K. The densities of the PDRs vary from 104–105 cm−3, reaching 3×105 cm−3 in some young compact PN. With a derived temperature of 1600 K and a density of 105 cm−3, the PDR of NGC 7027 is one of the warmest and at the same time one of the densest amongst the nebulae studied. For most of the PN studied, the [C II]-emitting regions contain only modest amounts of material, with gas masses ≲0.1 M⊙. Exceptional large PDR masses are found for a few nebulae, including NGC 7027, the bipolar nebulae M2-9 and NGC 6302, the young dense planetary nebulae BD+30°3639, IC 418 and NGC 5315, and the old, probably recombining, nebulae IC 4406 and NGC 6072

Immediate Surgical Repositioning Following Intrusive Luxation: A Case Report and Review of the Literature

This report presents a case of severe intrusive luxation of mature maxillary lateral incisor in a 10-year-old boy. The intruded tooth was immediately repositioned (surgical extrusion) and splinted within 2 h following injury. Tetracycline therapy was initiated at the time of repositioning and maintained for 10 days. Pulp removal and calcium hydroxide treatment of the root canal was carried out after repositioning. Splint was removed 1 month later. Definitive root canal treatment with gutta percha was accomplished at the second month recall. Clinical and radiographic examination 28 months after the surgical extrusion revealed satisfactory apical and periodontal healing

Towards a career in bioinformatics

The 2009 annual conference of the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation from 1998, was organized as the 8th International Conference on Bioinformatics (InCoB), Sept. 9-11, 2009 at Biopolis, Singapore. InCoB has actively engaged researchers from the area of life sciences, systems biology and clinicians, to facilitate greater synergy between these groups. To encourage bioinformatics students and new researchers, tutorials and student symposium, the Singapore Symposium on Computational Biology (SYMBIO) were organized, along with the Workshop on Education in Bioinformatics and Computational Biology (WEBCB) and the Clinical Bioinformatics (CBAS) Symposium. However, to many students and young researchers, pursuing a career in a multi-disciplinary area such as bioinformatics poses a Himalayan challenge. A collection to tips is presented here to provide signposts on the road to a career in bioinformatics. An overview of the application of bioinformatics to traditional and emerging areas, published in this supplement, is also presented to provide possible future avenues of bioinformatics investigation. A case study on the application of e-learning tools in undergraduate bioinformatics curriculum provides information on how to go impart targeted education, to sustain bioinformatics in the Asia-Pacific region. The next InCoB is scheduled to be held in Tokyo, Japan, Sept. 26-28, 2010

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity

Silk fibroin hydrogels crosslinked through di-tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light-mediated photoredox system for di-tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic-based crosslinking. This photomediated system rapidly crosslinks silk fibroin (80%). The photocrosslinked silk hydrogels present more stable mechanical properties which do not undergo spontaneous transition to stiff, β-sheet-rich networks typically seen for enzymatically crosslinked systems. These hydrogels also support long-term culture of human articular chondrocytes, with excellent cartilage tissue formation. This system also facilitates the first demonstration of biofabrication of silk fibroin constructs in the absence of chemical modification of the protein structure or rheological additives. Cell-laden constructs with complex, ordered, graduated architectures, and high resolution (40 µm) are fabricated using the photocrosslinking system, which cannot be achieved using the enzymatic crosslinking system. Taken together, this work demonstrates the immense potential of a new crosslinking approach for fabrication of elastomeric silk hydrogels with applications in biofabrication and tissue regeneration

Clinicians' attitude towards a placebo-controlled randomised clinical trial investigating the effect of neuraminidase inhibitors in adults hospitalised with influenza

Background: The value of neuraminidase inhibitors (NAIs) in reducing severe clinical outcomes from influenza is debated. A clinical trial to generate better evidence is desirable. However, it is unknown whether UK clinicians would support a placebo controlled trial. A survey was conducted to determine the attitude of clinicians towards a clinical trial and their current practice in managing adults admitted to hospital with suspected influenza. Methods: Senior clinicians (n=50) across the UK actively involved in the care of patients hospitalised with severe respiratory infections and/or respiratory infection research were invited to participate in an on-line survey. Participants were asked their opinion on the evidence for benefit of NAIs in influenza, their current practice in relation to: a) testing for influenza; b) treating empirically with NAIs; and c) when influenza infection is virolologically confirmed, prescribing NAIs. Results: Thirty-five (70%) of 50 clinicians completed the survey. Respondents were drawn mainly from infectious diseases, intensive care and respiratory medicine. Only 11 (31%) of 35 respondents agreed that NAIs are effective at reducing influenza mortality;14(40%)disagreed, 10 (28.6%) neither agreed nor disagreed. When managing adults admitted to non-ICU wards with a respiratory infection during an influenza season, 15 (51.7%) clinicians indicated they would usually perform a test for influenza in greater than 60% of patients but only 9 (31%) would treat empirically with NAIs in greater than 60% of patients. Few clinicians would either test or empirically treat patients presenting with other (non-respiratory infection related) diagnoses. If influenza infection is confirmed, 17 (64.5%) clinicians would prescribe NAIs in greater than 80% of patients with a respiratory infection treated on non-ICU wards Thirty-one (89%) clinicians agreed that a placebo-controlled clinical trial should be conducted and 29 (85%) would participate in such a trial. Conclusions: There is strong support from UK clinicians for a placebo-controlled trial of NAI treatment in adults hospitalised with suspected influenza. Current variation in medical opinion and clinical practice demonstrates collective equipoise, supporting ethical justification for a trial. Low use of NAIs in the UK suggests randomisation of treatment would not substantially divert patients towards placebo

Is it better to treat chronic hepatitis B as early as possible?—Con

Ideally, treatment of chronic hepatitis B in its early stage prior to irreversible liver damage should be most effective in preventing adverse clinical outcome. However, currently available treatments have low efficacy in achieving sustained response among patients in the early phase of chronic hepatitis B infection when the immune response to hepatitis B virus is weak. This review will provide evidence why a ‘wait and monitor’ approach is appropriate for chronic hepatitis B patients who are in the immune tolerant phase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73513/1/j.1440-1746.2004.03660.x.pd