Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Tropospheric emissions: Monitoring of pollution (TEMPO)

TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O), nitrogen dioxide (NO), sulfur dioxide (SO), formaldehyde (HCO), glyoxal (CHO), bromine monoxide (BrO), IO (iodine monoxide), water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O chemistry cycle. Multi-spectral observations provide sensitivity to O in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.Peer Reviewe

Metalloprotease Meprinβ in Rat Kidney: Glomerular Localization and Differential Expression in Glomerulonephritis

Meprin (EC 3.4.24.18) is an oligomeric metalloendopeptidase found in microvillar membranes of kidney proximal tubular epithelial cells. Here, we present the first report on the expression of meprinβ in rat glomerular epithelial cells and suggest a potential involvement in experimental glomerular disease. We detected meprinβ in glomeruli of immunostained rat kidney sections on the protein level and by quantitative RT-PCR of laser-capture microdissected glomeruli on the mRNA level. Using immuno-gold staining we identified the membrane of podocyte foot processes as the main site of meprinβ expression. The glomerular meprinβ expression pattern was altered in anti-Thy 1.1 and passive Heymann nephritis (PHN). In addition, the meprinβ staining pattern in the latter was reminiscent of immunostaining with the sheep anti-Fx1A antiserum, commonly used in PHN induction. Using Western blot and immunoprecipitation assays we demonstrated that meprinβ is recognized by Fx1A antiserum and may therefore represent an auto-antigen in PHN. In anti-Thy 1.1 glomerulonephritis we observed a striking redistribution of meprinβ in tubular epithelial cells from the apical to the basolateral side and the cytosol. This might point to an involvement of meprinβ in this form of glomerulonephritis

Estimating Contact Process Saturation in Sylvatic Transmission of Trypanosoma cruzi in the United States

Although it has been known for nearly a century that strains of Trypanosoma cruzi, the etiological agent for Chagas' disease, are enzootic in the southern U.S., much remains unknown about the dynamics of its transmission in the sylvatic cycles that maintain it, including the relative importance of different transmission routes. Mathematical models can fill in gaps where field and lab data are difficult to collect, but they need as inputs the values of certain key demographic and epidemiological quantities which parametrize the models. In particular, they determine whether saturation occurs in the contact processes that communicate the infection between the two populations. Concentrating on raccoons, opossums, and woodrats as hosts in Texas and the southeastern U.S., and the vectors Triatoma sanguisuga and Triatoma gerstaeckeri, we use an exhaustive literature review to derive estimates for fundamental parameters, and use simple mathematical models to illustrate a method for estimating infection rates indirectly based on prevalence data. Results are used to draw conclusions about saturation and which population density drives each of the two contact-based infection processes (stercorarian/bloodborne and oral). Analysis suggests that the vector feeding process associated with stercorarian transmission to hosts and bloodborne transmission to vectors is limited by the population density of vectors when dealing with woodrats, but by that of hosts when dealing with raccoons and opossums, while the predation of hosts on vectors which drives oral transmission to hosts is limited by the population density of hosts. Confidence in these conclusions is limited by a severe paucity of data underlying associated parameter estimates, but the approaches developed here can also be applied to the study of other vector-borne infections

Authority, Autonomy and Automation: The Irreducibility of Pedagogy to Information Transactions

"This paper draws attention to the tendency of a range of technologies to reduce pedagogical interactions to a series of datafied transactions of information. This is problematic because such transactions are always by definition reducible to finite possibilities. As the ability to gather and analyse data becomes increasingly fine-grained, the threat that these datafied approaches over-determine the pedagogical space increases. Drawing on the work of Hegel, as interpreted by 20th century French radical philosopher Alexandre Kojève, this paper develops a model of relational pedagogy which highlights three points of incompatibility with a datafied learning environment reduced to finite measures. Firstly: Kojève’s accont of authority in Hegel posits two aspects to the mimetic relation between teacher and student: recognition and realisation, which belong to the ipseity or about-self-ness of the subject, and are incompatible with a general definition of data. Secondly, the Hegelian approach to human historical time, in particular the assertion that time and desire are begun in the future, not the past, renders it incompatible with mathematical time as used in data processing. Finally, from these it is possible to derive a distinctive notion of the work of pedagogy, grounded in Kojève’s realist reading of Hegel, irreducible to information processing. In consequence of this threefold irreducibility, the paper draws attention to a need for relations of human pedagogical work to be inherent in the design of educational technologies and highlights the dangers of presuming a machine intelligence model in the design of learning environments.

A global horizon scan of the future impacts of robotics and autonomous systems on urban ecosystems

Technology is transforming societies worldwide. A major innovation is the emergence of robotics and autonomous systems (RAS), which have the potential to revolutionize cities for both people and nature. Nonetheless, the opportunities and challenges associated with RAS for urban ecosystems have yet to be considered systematically. Here, we report the findings of an online horizon scan involving 170 expert participants from 35 countries. We conclude that RAS are likely to transform land use, transport systems and human–nature interactions. The prioritized opportunities were primarily centred on the deployment of RAS for the monitoring and management of biodiversity and ecosystems. Fewer challenges were prioritized. Those that were emphasized concerns surrounding waste from unrecovered RAS, and the quality and interpretation of RAS-collected data. Although the future impacts of RAS for urban ecosystems are difficult to predict, examining potentially important developments early is essential if we are to avoid detrimental consequences but fully realize the benefits

Fyysisesti inaktiivisten opiskelijoiden motivaatio korkeaintensiteettisessä intervalliharjoittelussa

Tämän opinnäytetyön tarkoituksena oli selvittää fyysisesti inaktiivisten opiskeli-joiden kokemuksia sisäisestä ja ulkoisesta motivaatiosta ja harjoittelun mielek-kyydestä pyörällä toteutetussa korkeaintensiteettisessä intervalliharjoittelussa (Sprint interval training=SIT). Yhteistyökumppani opinnäytetyössä oli Saimaan korkeakoululiikunta, jonka yhdyshenkilönä toimi fysioterapeutti Hanna Bohm. Opinnäytetyö oli kvalitatiivinen, jossa aineisto kerättiin puolistrukturoiduilla teemahaastatteluilla. Opinnäytetyöstä laitettiin ilmoitus Saimaan korkeakoulu-liikunta SaLUT:n sivuille, jonka kautta vapaaehtoiset olivat yhteydessä opin-näytetyön tekijöihin. Vapaaehtoisista ja kriteerit täyttävistä hakijoista valittiin viisi henkilöä, joista lopulta neljä päätyi opinnäytetyöhön osallistujiksi. Osallis-tujat osallistuivat neljän viikon SIT–protokollan mukaiseen harjoitteluun kol-mena päivänä viikossa. Haastatteluista saadut tulokset analysoitiin käyttämällä induktiivista sisällönanalyysiä. Aineiston perusteella fyysisesti inaktiiviset opiskelijat kokivat sisäisiä ja ulkoisia motiiveja pyörällä toteutetussa korkeaintensiteettisessä intervalliharjoittelussa. Osallistujat kokivat harjoittelun mielekkääksi näkyvien harjoitusvasteiden, har-joituksen lyhytkestoisuuden ja fyysisten tuntemusten ansiosta. Osallistujia mo-tivoivat jatkamaan tuloksien näkyminen, oma hyvinvointi, onnistumisen koke-mukset ja mielenkiinto harjoitusmuotoa kohtaan. Jatkossa tutkimustuloksia voidaan hyödyntää esimerkiksi osana fysioterapiaprosessia fyysisesti inaktiivi-silla asiakkailla.The purpose of the thesis was to examine experiences of intrinsic and extrinsic motivation and reasonableness of training on physically inactive students in high intensity interval training implemented by cycle ergometer (Sprint interval training=SIT). The thesis was carried out in co-operation with Saimaan korkeakoululiikunta (Saimaa Higher Education Sports and Welfare Services). Physiotherapist Hanna Bohm from Saimaan korkeakoululiikunta acted as a contact person. The research method was qualitative and material was collected via semi-structured theme interviews. An advertisement was placed in the Saimaan korkeakoululiikunta website, inviting volunteers to contact the research team. Five people were selected among the volunteers and four ended up participat-ing in the study. The volunteers took part in intervention activities during four weeks, doing exercises according to the SIT–protocol three times a week. In-ductive content analysis was employed for analysing the answers received through interviews. According to the results, physically inactive students experienced both intrinsic and extrinsic motives in high intensity interval training implemented by cycle ergometer. Training was experienced enjoyable by the participants because of the exercise responses, short duration and physical sensations. The partici-pants were motivated to continue training because they saw the results and wanted to improve their wellbeing. Other motives to continue training were ex-periences of success and interest towards the training method. In the future the results can be used in physiotherapy processes with physically inactive clients, for example