2,897 research outputs found
P/Q-type calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: a functional genetic link for migraine?
No full textThe discovery of mis-sense mutations in the alpha1A subunit of the P/Q-type calcium channel in patients with familial hemiplegic migraine indicates the potential involvement of dysfunctional ion channels in migraine. The periaqueductal gray (PAG) region of the brainstem modulates craniovascular nociception and, through its role in the descending pain modulation system, may contribute to migraine pathophysiology. In this study we sought to investigate the possible link between the genetic mutations found in migraineurs and the PAG as a modulator of craniovascular nociception. We microinjected the P/Q-type calcium-channel blocker omega-agatoxin IVA into the rat ventrolateral PAG (vlPAG). We examined its effect on the nociceptive transmission of second-order neurons recorded in the trigeminal nucleus caudalis and activated by stimulation of the parietal dura mater. After injection of agatoxin into the vlPAG (n = 20) responses to dural stimulation were facilitated by 143% (p < 0.0001) for Adelta-fiber activity and 180% for C-fiber activity (p < 0.05). Similarly, spontaneous background activity increased by 163% (p < 0.0001). These results demonstrate that P/Q-type calcium channels in the PAG play a role in modulating trigeminal nociception and suggest a role for dysfunctional P/Q-type calcium channels in migraine pathophysiology.<br/
Primary cilia elongation in response to interleukin-1 mediates the inflammatory response
No full textPrimary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA
Book Discussion : PJ Powers
No full textThe UJ Campus Health Services and the Student Affairs Division in partnership with the UJ Library invite you to meet PJ Powers (Thandeka) the co-author of the book HERE I AM About the book: Here I Am, written with Marianne Thamm, is an intimate and hilarious account of the life and times of one of this country’s most recognisable and enduring performers. From the dizzying heights of international stardom to the dark depths of her struggle with alcohol, this is a must-read to explore the heady mix of politics and music of the time. More than just a story about the personal journey of one of South Africa’s most beloved music icons, this extraordinary memoir of PJ Powers – or Thandeka, as she was affectionately renamed by Soweto crowds – is set against the turbulent backdrop of South Africa’s recent political history. It features a gallery of political leaders and international celebrities, including the likes of Nelson Mandela, Graça Machel, Chris Hani, Joaquim Chissano, Queen Elizabeth II, Brenda Fassie, Sharon Stone and Robert De Niro. Facilitator: Prof Alban Burke, Director – PsyCad, University of Johannesburg PJ Powers will also perform a few songs on the day. Date: 27 August 2015 Time: 16:30 for 17:00 Venue: Auditorium (6th Floor), APK Library, University of Johannesburg (corner Kingsway and University Road, Auckland Park) RSVP: By Wednesday, 26 August 2015 to Theodorah Modise on [email protected] / 011 559 226
Book Discussion : PJ Powers
No full textThe UJ Campus Health Services and the Student Affairs Division in partnership with the UJ Library invite you to meet PJ Powers (Thandeka) the co-author of the book HERE I AM About the book: Here I Am, written with Marianne Thamm, is an intimate and hilarious account of the life and times of one of this country’s most recognisable and enduring performers. From the dizzying heights of international stardom to the dark depths of her struggle with alcohol, this is a must-read to explore the heady mix of politics and music of the time. More than just a story about the personal journey of one of South Africa’s most beloved music icons, this extraordinary memoir of PJ Powers – or Thandeka, as she was affectionately renamed by Soweto crowds – is set against the turbulent backdrop of South Africa’s recent political history. It features a gallery of political leaders and international celebrities, including the likes of Nelson Mandela, Graça Machel, Chris Hani, Joaquim Chissano, Queen Elizabeth II, Brenda Fassie, Sharon Stone and Robert De Niro. Facilitator: Prof Alban Burke, Director – PsyCad, University of Johannesburg PJ Powers will also perform a few songs on the day. Date: 27 August 2015 Time: 16:30 for 17:00 Venue: Auditorium (6th Floor), APK Library, University of Johannesburg (corner Kingsway and University Road, Auckland Park) RSVP: By Wednesday, 26 August 2015 to Theodorah Modise on [email protected] / 011 559 226
Viscoelastic Cell Mechanics and actin remodelling are dependent on the rate of applied pressure
No full textBackground: living cells are subjected to external and internal mechanical stresses. The effects of these stresses on the deformation and subsequent biological response of the cells remains unclear. This study tested the hypothesis that the rate at which pressure (or stress) is applied influence the viscoelastic properties of the cell associated with differences in the dynamics of the actin cytoskeleton.Principal finding: micropipette aspiration was used to determine the instantaneous and equilibrium moduli and the viscosity of isolated chondrocytes based on the standard linear solid (SLS) model and a variation of this incorporating Boltzmann superposition. Cells were visualised for 180 seconds following aspiration to 7 cmH2O at 0.35, 0.70 and 5.48 cmH2O/sec. Cell recovery was then examined for a further 180 seconds once the pressure had been removed. Reducing the rate of application of pressure reduced the levels of cell deformation and recovery associated with a significant increase in modulus and viscosity. Using GFP transfection and confocal microscopy, we show that chondrocyte deformation involves distortion, disassembly and subsequent reassembly of the cortical actin cytoskeleton. At faster pressure rates, cell deformation produced an increase in cell volume associated with membrane bleb formation. GFP-actin transfection inhibited the pressure rate dependent variation in cell mechanics indicating that this behaviour is regulated by GFP-sensitive actin dynamics.Conclusion: we suggest that slower rates of aspiration pressure enable greater levels of cortical actin distortion. This is partially inhibited by GFP or faster aspiration rates leading to membrane bleb formation and an increase in cell volume. Thus the rate of application of pressure regulates the viscoelastic mechanical properties of living cells through pressure rate sensitive differences in actin dynamics. Therefore cells appear softer when aspirated at a faster rate in contrast to what is expected of a normal viscoelastic materia
Technologically mediated learning: The future of training in Australia
No full textHosie, PJ ORCiD: 0000-0003-2585-024XFollowing a review of the economic imperatives currently facing Australia,
the future directions training will take are examined. Related training issues are considered; such as multiskilling, on-the-job training and legal issues. The author predicts that technologically mediated learning (TML),
especially interactive multimedia, will gain ascendancy as the predominant mode of delivery for training
Transfection of tissue transglutaminase into a highly malignant hamster fibrosarcoma leads to a reduced incidence of primary tumour growth
No full textA 0.7-V 0.43-pJ/cycle Wakeup Timer based on a Bang-bang Digital-Intensive frequency-Locked-Loop for IoT Applications
No full textA 40-nm CMOS wakeup timer employing a bang-bang digital-intensive frequency-locked loop for Internet-of-Things applications is presented. A self-biased ΣΔ digitally controlled oscillator (DCO) is locked to an RC time constant via a single-bit chopped comparator and a digital loop filter. Such highly digitized architecture fully exploits the advantages of advanced CMOS processes, thus enabling operation down to 0.7 V and a small area (0.07 mm 2 ). Most circuitry operates at 32× lower frequency than the DCO in order to reduce the total power consumption down to 181 nW. High frequency accuracy and a 10× enhancement of long-term stability is achieved by the adoption of chopping to reduce the effect of comparator offset and 1/f noise and by the use of ΣΔ modulation to improve the DCO resolution. The proposed timer achieves the best energy efficiency (0.43 pJ/cycle at 417 kHz) over prior art while keeping excellent on-par long-term stability (Allan deviation floor <;20 ppm) and temperature stability (106 ppm/°C).Accepted Author Manuscript(OLD)Applied Quantum Architecture
Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.
No full textBACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation
EFEKTIVITAS PASAL 1 PERATURAN DIREKTUR JENDRAL PAJAK NOMOR PER-18/PJ/2017
No full textTahap Penelitian atau yang penulis biasa sebut dengan validasi SSP (Surat Setoran Pajak) merupakan tahap final dimana seorang wajib pajak telah melakukan kewajibannya dalam penyetoran pajak, dan dalam proses validasi itu sendiri tidak semua akan diterima oleh kantor pajak setempat karena masih akan dilakukan penelitian baik penelitian serara formil maupun materiil. Untuk mekanismenya validasi telah ditetapkan dalam Per-18/Pj/2017 Tentang Cara Penelitian Bukti Pemenuhan Kewajiban Penyetoran Pajak Penghasilan Atas Penghasilan Dari Pengalihan Hak Atas Tanah Dan/Atau Bangunan, Dan Perjanjian Pengikatan Jual Beli Atas Tanah Dan/Atau Bangunan Beserta Perubahannya. Efektifitas pasal 1 Peraturan Direktur Jendral Pajak Nomor Per-18/Pj/2017 di Kantor Pajak Pratama Kota Malang telah sesuai akan tetapi untuk pasal 1 ayat 2 masih belum dan untuk pengikatan jual beli, dan mengenai cara pembuktian bahwa wajib pajak telah memenuhi kewajiban penyetoran adalah dengan cara validasi ataupun telah di telitiKata Kunci: kewajiban, penyetoran, pemenuhan, pajak, validasiThe Research Phase or what the author commonly refers to as SSP validation (Tax Payment Deposit) is the final stage in which a taxpayer has carried out his obligations in tax payments, and in the process of validation itself not all will be accepted by the local tax office because there will still be done a research both formal and material. For the mechanism of validation, it has been stipulated in Per-18 / Pj / 2017 Regarding the Method of Research of Evidence of Fulfillment of Obligation of Income Tax on Income from Transfer of Land and / or Building Rights, and Agreement on Binding of Sale and Purchase of Land and / or Buildings and Amendments. The effectiveness of article 1 of the Regulation of the Director General of Tax Number Per-18 / Pj / 2017 in the Pratama Tax Office Malang is appropriate but for article 1 paragraph 2 it is still not yet for the binding of buying and selling, and regarding the means of proving that the taxpayer has fulfilled the payment obligation is by validation or thoroughlyKeywords: oblilgation, deposit, fulfillment, tax, validatio
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