RESUMO
We explore peoples' dispositions and practices with regard to social-ecological transformations based on a sustainable welfare policy strategy in Sweden. We draw on Bourdieu's concept of habitus to highlight the relations between social positions, dispositions, and position-takings. Using data from an own survey, we identify habitus types and place these in the space of social positions. We apply principal component analysis to a large set of questions about social, ecological, and climate change related topics and identify eight underlying eco-social dispositions. These are used for cluster analyses that find typical constellations of eco-social dispositions within the Swedish population: variants of eco-social habitus. We find seven habitus types and describe their social characteristics, political preferences, and practices. Finally, the seven habitus are plotted onto the map of social positions, the Bourdieusian social space, highlighting their relations-proximities, tensions, and contestations-to each other. We find evidence that political struggles around social-ecological transformations reproduce existing social structures but are also connected to new "eco-social" divisions that appear between groups in similar positions. In the conclusion we discuss the implications for social-ecological transformations based on sustainable welfare.
Assuntos
Mudança Climática , Meio Social , Humanos , SuéciaRESUMO
Slit proteins are secreted ligands that interact with the Roundabout (Robo) receptors to provide important guidance cues in neuronal and vascular development. Slit-Robo signalling is mediated by an interaction between the second Slit domain and the first Robo domain, as well as being dependent on heparan sulphate. In an effort to understand the role of the other Slit domains in signalling, we determined the crystal structure of the fourth Slit2 domain (D4) and examined the effects of various Slit2 constructs on chick retinal ganglion cell axons. Slit2 D4 forms a homodimer using the conserved residues on its concave face, and can also bind to heparan sulphate. We observed that Slit2 D4 frequently results in growth cones with collapsed lamellipodia and that this effect can be inhibited by exogenously added heparan sulphate. Our results show that Slit2 D4-heparan sulphate binding contributes to a Slit-Robo signalling mechanism more intricate than previously thought.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Multimerização Proteica , Sequência Conservada , Decorina , Proteínas da Matriz Extracelular/química , Heparitina Sulfato/metabolismo , Humanos , Modelos Moleculares , Estrutura Terciária de Proteína , Proteoglicanas/química , Homologia de Sequência de Aminoácidos , Eletricidade Estática , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: Diabetes patients are increasingly using a continuous glucose sensor to monitor blood glucose and an insulin pump connected to an infusion cannula to administer insulin. Applying these devices requires two separate insertion sites, one for the sensor and one for the cannula. Integrating sensor with cannula to perform glucose sensing and insulin infusion through a single insertion site would significantly simplify and improve diabetes treatment by reducing the overall system size and the number of necessary needle pricks. Presently, several research groups are pursuing the development of combined glucose sensing and insulin infusion devices, termed single-port devices, by integrating sensing and infusion technologies created from scratch. METHODS: Instead of creating the device from scratch, we utilized already existing technologies and introduced three design concepts of integrating commercial glucose sensors and infusion cannulas. We prototyped and evaluated each concept according to design simplicity, ease of insertion, and sensing accuracy. RESULTS: We found that the best single-port device is the one in which a Dexcom sensor is housed inside a Medtronic cannula so that its glucose sensitive part protrudes from the cannula tip. The low degree of component modification required to arrive at this configuration allowed us to test the efficiency and safety of the device in humans. CONCLUSION: Results from these studies indicate the feasibility of combining commercial glucose sensing and insulin delivery technologies to realize a functional single-port device. SIGNIFICANCE: Our development approach may be generally useful to provide patients with innovative medical devices faster and at reduced costs.
Assuntos
Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Glicemia/análise , Desenho de Equipamento , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pâncreas ArtificialRESUMO
OBJECTIVE: This study evaluated a novel diabetes treatment device that combines commercially available continuous glucose monitoring and insulin infusion technology in such a way as to perform insulin delivery and glucose sensing through a single skin insertion site (single-port device). METHODS: Ten type 1 diabetes patients used the device for up to six days in their home/work environment for open-loop insulin delivery and glucose sensing. On an additional day, the device was used in combination with an algorithm to perform automated closed-loop glucose control under hospital settings. To assess the performance of the device, capillary blood glucose concentrations were frequently determined and a continuous glucose sensor was additionally worn by the patients. RESULTS: The average mean absolute relative deviation from blood glucose concentrations obtained for the sensor of the device was low (median, 13.0%; interquartile range, 10.5-16.7%; n = 10) and did not differ from that of the additionally worn glucose sensor (versus 13.9%; 11.9-15.3%; P = 0.922). Furthermore, insulin delivery with the single-port device was reliable and safe during home use and, when performed in combination with the control algorithm, was adequate to achieve and maintain near normoglycemia. CONCLUSION: Our data show the feasibility of open- and closed-loop glucose control in diabetes patients using a device that combines insulin delivery and glucose sensing at a single tissue site. SIGNIFICANCE: The reduction in device size and invasiveness achieved by this design may largely increase patient convenience and enhance acceptance of diabetes treatment with continuous glucose monitoring and insulin delivery technology.
Assuntos
Automonitorização da Glicemia/instrumentação , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Pâncreas Artificial , Adolescente , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The function and regulation of amyloid-beta (Aß) in healthy and diseased liver remains unexplored. Because Aß reduces the integrity of the blood-brain barrier we have examined its potential role in regulating the sinusoidal permeability of normal and cirrhotic liver. Aß and key proteins that generate (beta-secretase 1 and presenilin-1) and degrade it (neprilysin and myelin basic protein) were decreased in human cirrhotic liver. In culture, activated hepatic stellate cells (HSC) internalized Aß more efficiently than astrocytes and HSC degraded Aß leading to suppressed expression of α-smooth muscle actin (α-SMA), collagen 1 and transforming growth factor ß (TGFß). Aß also upregulated sinusoidal permeability marker endothelial NO synthase (eNOS) and decreased TGFß in cultured human liver sinusoidal endothelial cells (hLSEC). Liver Aß levels also correlate with the expression of eNOS in transgenic Alzheimer's disease mice and in human and rodent cirrhosis/fibrosis. These findings suggest a previously unexplored role of Aß in the maintenance of liver sinusoidal permeability and in protection against cirrhosis/fibrosis via attenuation of HSC activation.
Assuntos
Peptídeos beta-Amiloides/uso terapêutico , Fibrose/tratamento farmacológico , Expressão Gênica/genética , Cirrose Hepática/terapia , Fragmentos de Peptídeos/uso terapêutico , Peptídeos beta-Amiloides/farmacologia , Animais , Modelos Animais de Doenças , Humanos , Cirrose Hepática/fisiopatologia , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues. Computational modeling suggests that topographic accuracy and adaptability, though seemingly incompatible, could be reconciled by a novel mechanism of coupled adaptation of signaling channels. Experimentally, we find such 'co-adaptation' in retinal growth cones specifically for ephrin-A/EphA signaling. Co-adaptation involves trafficking of unliganded sensors between the surface membrane and recycling endosomes, and is presumably triggered by changes in the lipid composition of membrane microdomains. We propose that co-adaptative desensitization eventually relies on guidance sensor translocation into cis-signaling endosomes to outbalance repulsive trans-signaling.
Assuntos
Orientação de Axônios , Efrinas/metabolismo , Cones de Crescimento/fisiologia , Receptores da Família Eph/metabolismo , Retina/embriologia , Células Ganglionares da Retina/fisiologia , Animais , Embrião de Galinha , Simulação por Computador , Endossomos/metabolismo , Proteínas de Membrana/metabolismoRESUMO
Long-term vibration stress can contribute to degenerative changes in the joints of the human body, especially in the lumbar spine. An important factor in the development of these diseases is given by the forces transmitted in the joints. Because the forces can hardly be measured a biomechanical model was developed which simulates the human body in the standing and the sitting posture. The vibration properties of the model were adapted to the transfer function provided in the standards and the literature. With the model the compressive forces at the driving point of the body, in the leg joints, and in two motion segments of the spine were simulated under a vertical pseudo random vibration. Transfer functions between the accelerations of the ground or of the seat and the forces were computed. Furthermore, based on the transfer function between seat acceleration and compressive force in the spinal motion segment L3-L4 weighting factors were derived. By means of these factors characteristic vibration values were computed for 57 realistic vibration spectra measured on 17 machines and vehicles. The consideration of the forces resulted in a stronger weighting of low-frequency vibrations compared to the weighted acceleration as suggested by ISO 2631-1. In order to enable an assessment of the health risk a force-related guidance value was derived which amounts to 0.81 ms(-2) (rms).
Assuntos
Dor Lombar/etiologia , Vibração/efeitos adversos , Fenômenos Biomecânicos , Ergonomia , Alemanha , Humanos , Dor Lombar/prevenção & controle , Medição de Risco , Estados UnidosRESUMO
Patterned distributions of signalling molecules play fundamental roles during embryonic development. Several attempts have been made to reproduce these patterns in vitro. In order to study substrate-bound or membrane proteins, microcontact printing (µCP) is a suitable method for tethering molecules on various surfaces. Here, we describe three µCP variants to produce patterns down to feature sizes of about 300 nm, which are highly variable with respect to shape, protein spacing, and density. Briefly, the desired pattern is etched into a silicon master, which is then used as a master for the printing process. Each variant offers certain advantages and the method of choice depends on the desired protein and the biological question.
Assuntos
Técnicas de Cultura de Células/métodos , Impressão/métodos , Proteínas/metabolismo , Técnicas de Cultura de Tecidos/métodos , Animais , Dimetilpolisiloxanos/química , Fluorescência , Ouro/química , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/metabolismo , Silício/química , Compostos de Sulfidrila/químicaRESUMO
By means of a four-degrees-of-freedom model the vertical movements of an athlete and the time course of the ground reaction force were simulated during a countermovement jump on a concrete and a wooden surface. The model masses were connected to each other and to the surface by springs and dampers. At first the stiffness of the springs decreased in order to initiate the countermovement. Afterwards the stiffness increased like the muscle activity so that the flexion of the model 'legs' were decelerated before the extension starts. The best result was attained when the stiffness of the spring between the model masses 'thighs' and 'trunk' increased before the other three springs. Compared with the muscle activity this means that for a successful jump the upper body segments have to be accelerated before the segments near to the ground are accelerated. The model 'athlete' was connected to a model of the surface. It could be shown that the jump on a concrete surface results in a better jump height than the jump on an elastic wooden surface if the muscle activation is not adapted to the surface properties.