Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells

BACKGROUND: Spatio-temporal control of extracellular signal-regulated kinase (ERK) activity, a critical determinant of the cell's response to growth factors, requires timely dephosphorylation of its regulatory tyrosine and/or threonine residue by MAPK phosphatases. We studied the physiological role of kinase interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) in the control of EGF- and NGF-induced ERK activity in neuroendocrine PC12 cells. RESULTS: We found a single KIM-containing PTP to be endogenously expressed in rat PC12 cells: the transmembrane PTPRR isoform termed PCPTP1. Protein knock-down of PCPTP1, or fourfold overexpression of its mouse orthologue, PTPBR7, left EGF- and NGF-induced ERK1/2 activity in PC12 cells unaltered. Ectopic expression of cytosolic PTPRR isoforms, however, resulted in reduced EGF-induced ERK1/2 activity, an effect that was dependent on the phosphatase activity and the KIM-domain of these PTPs. CONCLUSION: The finding that robust changes in tyrosine-specific MAPK phosphatase expression levels have minor effects on temporal ERK1/2 activity control in PC12 cells suggests that dual-specificity MAPK phosphatases may act as major regulators of growth factor-induced ERK1/2 signaling in these cells

Inflammatory cytokines in an experimental model for the multiple organ dysfunction syndrome

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Capture of CO2 from medium-scale emission sources

AbstractUntil now, the work done on capture and storage of CO2 has mainly focused on capture and storage of CO2 from fossil fuel fired power plants and other large point sources. Although medium-scale sources of CO2 account for a smaller proportion, their contribution to global CO2 emissions is still substantial and in the range of 10–15% of total global energy related CO2 emissions. The study identifies possible combinations of capture technologies and medium scale combustion installations and assesses these in terms of potential and costs. Although medium-scale capture of CO2 is expected to be more expensive than large-scale capture, it may nevertheless be competitive with alternative methods of abating CO2 from medium-scale sources in some circumstances

Increasing cytotoxic activity and production of reactive oxygen and nitrogen intermediates by peritoneal macrophages during the development of multiple organ dysfunction syndrome in mice

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Opportunities for CO2 capture through oxygen conducting membranes at medium-scale oxyfuel coal boilers

AbstractEcofys and ECN conducted a study commissioned by the IEA Greenhouse Gas R&D Programme to identify the most suitable combinations of medium-scale CO2 sources (1–100 MWth) and capture technologies, with respect to potential and costs (see parallel paper by Hendriks et al.). An industrial coal-fired Circulating Fluidized Bed (CFB) boiler with oxyfuel combustion and Oxygen Conducting Membranes (OCM) appeared to be an economically attractive combination to capture CO2. This paper describes the principle and economic evaluation of this combination in comparison with a reference coal boiler without CO2 capture, as well as a coal boiler with CO2 capture based on amine scrubbing

Strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilisation each reduce pain and disability in people with knee osteoarthritis: a systematic review

QuestionWhat are the effects of strength training alone, exercise therapy alone, and exercise with additional passive manual mobilisation on pain and function in people with knee osteoarthritis compared to control? What are the effects of these interventions relative to each other?DesignA meta-analysis of randomised controlled trials.ParticipantsAdults with osteoarthritis of the knee.Intervention typesStrength training alone, exercise therapy alone (combination of strength training with active range of motion exercises and aerobic activity), or exercise with additional passive manual mobilisation, versus any non-exercise control. Comparisons between the three interventions were also sought.Outcome measuresThe primary outcome measures were pain and physical function.Results12 trials compared one of the interventions against control. The effect size on pain was 0.38 (95% CI 0.23 to 0.54) for strength training, 0.34 (95% CI 0.19 to 0.49) for exercise, and 0.69 (95% CI 0.42 to 0.96) for exercise plus manual mobilisation. Each intervention also improved physical function significantly. No randomised comparisons of the three interventions were identified. However, meta-regression indicated that exercise plus manual mobilisations improved pain significantly more than exercise alone (p = 0.03). The remaining comparisons between the three interventions for pain and physical function were not significant.ConclusionExercise therapy plus manual mobilisation showed a moderate effect size on pain compared to the small effect sizes for strength training or exercise therapy alone. To achieve better pain relief in patients with knee osteoarthritis physiotherapists or manual therapists might consider adding manual mobilisation to optimise supervised active exercise programs

Transcription-Dependent Cytosine Deamination Is a Novel Mechanism in Ultraviolet Light-Induced Mutagenesis

SummarySkin cancer is the most ubiquitous cancer type in the Caucasian population, and its incidence is increasing rapidly [1]. Transcribed proliferation-related genes in dermal stem cells are targets for the induction of ultraviolet light (UV)-induced mutations that drive carcinogenesis. We have recently found that transcription of a gene increases its mutability by UV in mammalian stem cells, suggesting a role of transcription in skin carcinogenesis [2]. Here we show that transcription-associated UV-induced nucleotide substitutions are caused by increased deamination of cytosines to uracil within photolesions at the transcribed strand, presumably at sites of stalled transcription complexes. Additionally, via an independent mechanism, transcription of UV-damaged DNA induces the generation of intragenic deletions. We demonstrate that transcription-coupled nucleotide excision repair (TC-NER) provides protection against both classes of transcription-associated mutagenesis. Combined, these results unveil the existence of two mutagenic pathways operating specifically at the transcribed DNA strand of active genes. Moreover, these results uncover a novel role for TC-NER in the suppression of UV-induced genome aberrations and provide a rationale for the efficient induction of apoptosis by stalled transcription complexes