937 resultados para drive-by
Resumo:
Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.
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Neutropenia is probably the strongest known predisposition to infection with otherwise harmless environmental or microbiota-derived species. Because initial swarming of neutrophils at the site of infection occurs within minutes, rather than the hours required to induce "emergency granulopoiesis," the relevance of having high numbers of these cells available at any one time is obvious. We observed that germ-free (GF) animals show delayed clearance of an apathogenic bacterium after systemic challenge. In this article, we show that the size of the bone marrow myeloid cell pool correlates strongly with the complexity of the intestinal microbiota. The effect of colonization can be recapitulated by transferring sterile heat-treated serum from colonized mice into GF wild-type mice. TLR signaling was essential for microbiota-driven myelopoiesis, as microbiota colonization or transferring serum from colonized animals had no effect in GF MyD88(-/-)TICAM1(-/-) mice. Amplification of myelopoiesis occurred in the absence of microbiota-specific IgG production. Thus, very low concentrations of microbial Ags and TLR ligands, well below the threshold required for induction of adaptive immunity, sets the bone marrow myeloid cell pool size. Coevolution of mammals with their microbiota has probably led to a reliance on microbiota-derived signals to provide tonic stimulation to the systemic innate immune system and to maintain vigilance to infection. This suggests that microbiota changes observed in dysbiosis, obesity, or antibiotic therapy may affect the cross talk between hematopoiesis and the microbiota, potentially exacerbating inflammatory or infectious states in the host.
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Cathodoluminescence (CL) studies have previously shown that some secondary fluid inclusions in luminescent quartz are surrounded by dark, non-luminescent patches, resulting from fracture-sealing by late, trace-element-poor quartz. This finding has led to the tacit generalization that all dark CL patches indicate influx of low temperature, late-stage fluids. In this study we have examined natural and synthetic hydrothermal quartz crystals using CL imaging supplemented by in-situ elemental analysis. The results lead us to propose that all natural, liquid-water-bearing inclusions in quartz, whether trapped on former crystal growth surfaces (i.e., of primary origin) or in healed fractures (i.e., of pseudosecondary or secondary origin), are surrounded by three-dimensional, non-luminescent patches. Cross-cutting relations show that the patches form after entrapment of the fluid inclusions and therefore they are not diagnostic of the timing of fluid entrapment. Instead, the dark patches reveal the mechanism by which fluid inclusions spontaneously approach morphological equilibrium and purify their host quartz over geological time. Fluid inclusions that contain solvent water perpetually dissolve and reprecipitate their walls, gradually adopting low-energy euhedral and equant shapes. Defects in the host quartz constitute solubility gradients that drive physical migration of the inclusions over distances of tens of μm (commonly) up to several mm (rarely). Inclusions thus sequester from their walls any trace elements (e.g., Li, Al, Na, Ti) present in excess of equilibrium concentrations, thereby chemically purifying their host crystals in a process analogous to industrial zone refining. Non-luminescent patches of quartz are left in their wake. Fluid inclusions that contain no liquid water as solvent (e.g., inclusions of low-density H2O vapor or other non-aqueous volatiles) do not undergo this process and therefore do not migrate, do not modify their shapes with time, and are not associated with dark-CL zone-refined patches. This new understanding has implications for the interpretation of solids within fluid inclusions (e.g., Ti- and Al-minerals) and for the elemental analysis of hydrothermal and metamorphic quartz and its fluid inclusions by microbeam methods such as LA-ICPMS and SIMS. As Ti is a common trace element in quartz, its sequestration by fluid inclusions and its depletion in zone-refined patches impacts on applications of the Ti-in-quartz geothermometer.
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There is considerable evidence that biodiversity promotes multiple ecosystem functions (multifunctionality), thus ensuring the delivery of ecosystem services important for human well-being. However, the mechanisms underlying this relationship are poorly understood, especially in natural ecosystems. We develop a novel approach to partition biodiversity effects on multifunctionality into three mechanisms and apply this to European forest data. We show that throughout Europe, tree diversity is positively related with multifunctionality when moderate levels of functioning are required, but negatively when very high function levels are desired. For two well-known mechanisms, ‘complementarity’ and ‘selection’, we detect only minor effects on multifunctionality. Instead a third, so far overlooked mechanism, the ‘jack-of-all-trades’ effect, caused by the averaging of individual species effects on function, drives observed patterns. Simulations demonstrate that jack-of-all-trades effects occur whenever species effects on different functions are not perfectly correlated, meaning they may contribute to diversity–multifunctionality relationships in many of the world’s ecosystems.
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An increase in carbon dioxide (CO2) and protons (H+) are the primary signals for breathing. Cells that sense changes in CO2/H+ levels and increase breathing accordingly are located in a region of the caudal medulla oblongata called the retrotrapezoid nucleus (RTN). Specifically, select RTN neurons are intrinsically pH sensitive and send excitatory projections to the respiratory rhythm generator to drive breathing. Glial cells in the RTN are thought to contribute to this respiratory drive, possibly by releasing ATP in response to increases in CO2/H+ levels. However, pH sensitivity of RTN glial cells has yet to be determined. Therefore, the goal of my thesis is to determine if acutely dissociated RTN cells can respond to changes in pH in isolation. To make this determination I used ratiometric fluorescent microscopy to measure intracellular calcium in dissociated RTN cells during changes in bath pH. I found that a small percentage of RTN cells (16%) respond to bath acidification from pH 7.3 to pH 6.9 with an increase in fluorescence indicating an increase in intracellular calcium. Preliminary electrophysiological findings suggest that responsive cells are unable to make action potentials, thus suggesting their identity to be glia. These results indicate that a subset of pH sensitive cells in the RTN are intrinsically pH sensitive and that glia cells may possibly play a role in central chemoreception.
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Cells govern their activities and modulate their interactions with the environment to achieve homeostasis. The heat shock response (HSR) is one of the most well studied fundamental cellular responses to environmental and physiological challenges, resulting in rapid synthesis of heat shock proteins (HSPs), which serve to protect cellular constituents from the deleterious effects of stress. In addition to its role in cytoprotection, the HSR also influences lifespan and is associated with a variety of human diseases including cancer, aging and neurodegenerative disorders. In most eukaryotes, the HSR is primarily mediated by the highly conserved transcription factor HSF1, which recognizes target hsp genes by binding to heat shock elements (HSEs) in their promoters. In recent years, significant efforts have been made to identify small molecules as potential pharmacological activators of HSF1 that could be used for therapeutic benefit in the treatment of human diseases relevant to protein conformation. However, the detailed mechanisms through which these molecules drive HSR activation remain unclear. In this work, I utilized the baker's yeast Saccharomyces cerevisiae as a model system to identify a group of thiol-reactive molecules including oxidants, transition metals and metalloids, and electrophiles, as potent activators of yeast Hsf1. Using an artificial HSE-lacZ reporter and the glucocorticoid receptor system (GR), these diverse thiol-reactive compounds are shown to activate Hsf1 and inhibit Hsp90 chaperone complex activity in a reciprocal, dose-dependent manner. To further understand whether cells sense these reactive compounds through accumulation of unfolded proteins, the proline analog azetidine-2-carboxylic acid (AZC) and protein cross-linker dithiobis(succinimidyl propionate) (DSP) were used to force misfolding of nascent polypeptides and existing cytosolic proteins, respectively. Both unfolding reagents display kinetic HSP induction profiles dissimilar to those generated by thiol-reactive compounds. Moreover, AZC treatment leads to significant cytotoxicity, which is not observed in the presence of the thiol-reactive compounds at the concentrations sufficient to induce Hsf1. Additionally, DSP treatment has little to no effect on Hsp90 functions. Together with the ultracentrifugation analysis of cell lysates that detected no insoluble protein aggregates, my data suggest that at concentrations sufficient to induce Hsf1, thiol-reactive compounds do not induce the HSR via a mechanism based on accumulation of unfolded cytosolic proteins. Another possibility is that thiol-reactive compounds may influence aspects of the protein quality control system such as the ubiquitin-proteasome system (UPS). To address this hypothesis, β-galactosidase reporter fusions were used as model substrates to demonstrate that thiol-reactive compounds do not inhibit ubiquitin activating enzymes (E1) or proteasome activity. Therefore, thiol-reactive compounds do not activate the HSR by inhibiting UPS-dependent protein degradation. I therefore hypothesized that these molecules may directly inactivate protein chaperones, known as repressors of Hsf1. To address this possibility, a thiol-reactive biotin probe was used to demonstrate in vitro that the yeast cytosolic Hsp70 Ssa1, which partners with Hsp90 to repress Hsf1, is specifically modified. Strikingly, mutation of conserved cysteine residues in Ssa1 renders cells insensitive to Hsf1 activation by cadmium and celastrol but not by heat shock. Conversely, substitution with the sulfinic acid and steric bulk mimic aspartic acid led to constitutive activation of Hsf1. Cysteine 303, located in the nucleotide-binding/ATPase domain of Ssa1, was shown to be modified in vivo by a model organic electrophile using Click chemistry technology, verifying that Ssa1 is a direct target for thiol-reactive compounds through adduct formation. Consistently, cadmium pretreatment promoted cells thermotolerance, which is abolished in cells carrying SSA1 cysteine mutant alleles. Taken together, these findings demonstrate that Hsp70 acts as a sensor to induce the cytoprotective heat shock response in response to environmental or endogenously produced thiol-reactive molecules and can discriminate between two distinct environmental stressors.
Resumo:
El propósito de esta ponencia, es realizar un análisis del gesto técnico denominado "Drive", golpe determinante en la disciplina de Pelota a Paleta, a partir del estudio Anatómico y Biomecánico de la articulación Glenohumeral. Se destacará la importancia de los conocimientos anatomo-funcionales en la formación del Profesor en Educación Física, como base para el análisis del movimiento en cuestión, ya sea con fines de rendimiento deportivo o para mejorar la intervención docente. La articulación Glenohumeral es parte de un complejo de articulaciones que corresponde a la Cintura Escapular. Esta, posee 3 grados de libertad, lo que permite orientar al miembro superior en relación a los 3 planos del espacio, a disposición de tres ejes principales, y de esa manera, combinarlos gracias a su característica de articulación en esfera (Diartrosis-Enartrosis). A partir de Aquí, los movimientos principales que puede realizar son: La Flexión y la Extensión en el plano Sagital en torno al eje transversal; la Aducción y la Abducción en el plano frontal con su eje anteroposterior; la Rotación Interna y la Rotación Externa en el plano horizontal, alrededor del eje vertical, y por último, el movimiento de circunduccion, que resulta de la combinación de los precedentes. Los principios básicos para el desarrollo del golpe, establecen que éste debe comenzar desde la empuñadura de la paleta, la posición del cuerpo en sus diferentes instancias, hasta llegar al momento del golpe para realizar un correcto impacto. Este último momento se realiza llevando el miembro superior desde atrás hacia delante, con el codo extendido en el momento del golpeo y a la altura del hombro. Es un golpe para imprimir fuerza y dirección a la pelota
Resumo:
El propósito de esta ponencia, es realizar un análisis del gesto técnico denominado "Drive", golpe determinante en la disciplina de Pelota a Paleta, a partir del estudio Anatómico y Biomecánico de la articulación Glenohumeral. Se destacará la importancia de los conocimientos anatomo-funcionales en la formación del Profesor en Educación Física, como base para el análisis del movimiento en cuestión, ya sea con fines de rendimiento deportivo o para mejorar la intervención docente. La articulación Glenohumeral es parte de un complejo de articulaciones que corresponde a la Cintura Escapular. Esta, posee 3 grados de libertad, lo que permite orientar al miembro superior en relación a los 3 planos del espacio, a disposición de tres ejes principales, y de esa manera, combinarlos gracias a su característica de articulación en esfera (Diartrosis-Enartrosis). A partir de Aquí, los movimientos principales que puede realizar son: La Flexión y la Extensión en el plano Sagital en torno al eje transversal; la Aducción y la Abducción en el plano frontal con su eje anteroposterior; la Rotación Interna y la Rotación Externa en el plano horizontal, alrededor del eje vertical, y por último, el movimiento de circunduccion, que resulta de la combinación de los precedentes. Los principios básicos para el desarrollo del golpe, establecen que éste debe comenzar desde la empuñadura de la paleta, la posición del cuerpo en sus diferentes instancias, hasta llegar al momento del golpe para realizar un correcto impacto. Este último momento se realiza llevando el miembro superior desde atrás hacia delante, con el codo extendido en el momento del golpeo y a la altura del hombro. Es un golpe para imprimir fuerza y dirección a la pelota
Resumo:
El propósito de esta ponencia, es realizar un análisis del gesto técnico denominado "Drive", golpe determinante en la disciplina de Pelota a Paleta, a partir del estudio Anatómico y Biomecánico de la articulación Glenohumeral. Se destacará la importancia de los conocimientos anatomo-funcionales en la formación del Profesor en Educación Física, como base para el análisis del movimiento en cuestión, ya sea con fines de rendimiento deportivo o para mejorar la intervención docente. La articulación Glenohumeral es parte de un complejo de articulaciones que corresponde a la Cintura Escapular. Esta, posee 3 grados de libertad, lo que permite orientar al miembro superior en relación a los 3 planos del espacio, a disposición de tres ejes principales, y de esa manera, combinarlos gracias a su característica de articulación en esfera (Diartrosis-Enartrosis). A partir de Aquí, los movimientos principales que puede realizar son: La Flexión y la Extensión en el plano Sagital en torno al eje transversal; la Aducción y la Abducción en el plano frontal con su eje anteroposterior; la Rotación Interna y la Rotación Externa en el plano horizontal, alrededor del eje vertical, y por último, el movimiento de circunduccion, que resulta de la combinación de los precedentes. Los principios básicos para el desarrollo del golpe, establecen que éste debe comenzar desde la empuñadura de la paleta, la posición del cuerpo en sus diferentes instancias, hasta llegar al momento del golpe para realizar un correcto impacto. Este último momento se realiza llevando el miembro superior desde atrás hacia delante, con el codo extendido en el momento del golpeo y a la altura del hombro. Es un golpe para imprimir fuerza y dirección a la pelota
Resumo:
Studies in the fission yeast Schizosaccharomyces pombe (S. pombe) have done much to inform the view of heterochromatin and its control by the RNA interference (RNAi) machinery. Using cDNA synthesised from poly(A)-enriched RNA samples, numerous novel ncRNA loci were discovered, and the 50 and 30 ends of many other genes were refined in previous studies. Although some of these transcripts may encode novel proteins the function of the majority is yet to be determined. The authors have used strand-specific deep sequencing of RNA, irrespective of poly(A) status, to reveal a highly structured antisense programme that modulates gene expression to dictate cell fate decisions during sexual differentiation. They show that an extensive and elaborate array of ncRNA production accompanies sexual differentiation in the fission yeast S. pombe. Experimental manipulation suggests that these transcripts specifically regulate the function of the target genes.
Resumo:
Ocean acidification (OA) is expected to drive the transition of coral reef ecosystems from net calcium carbonate (CaCO3) precipitating to net dissolving within the next century. Although permeable sediments represent the largest reservoir of CaCO3 in coral reefs, the dissolution of shallow CaCO3 sands under future pCO2 levels has not been measured under natural conditions. In situ, advective chamber incubations under elevated pCO2 (~800 µatm) shifted the sediments from net precipitating to net dissolving. Pore water advection more than doubled dissolution rates (1.10 g CaCO3/m**2/day) when compared to diffusive conditions (0.42 g CaCO3/m**2 /day). Sediment dissolution could reduce net ecosystem calcification rates of the Heron Island lagoon by 8% within the next century, which is equivalent to a 25% reduction in the global average calcification rate of coral lagoons. The dissolution of CaCO3 sediments needs to be taken into account in order to address how OA will impact the net accretion of coral reefs under future predicted increases in CO2.
Resumo:
The coccolithophore Emiliania huxleyi is a marine phytoplankton species capable of forming small calcium carbonate scales (coccoliths) which cover the organic part of the cell. Calcification rates of E. huxleyi are known to be sensitive to changes in seawater carbonate chemistry. It has, however, not yet been clearly determined how these changes are reflected in size and weight of individual coccoliths and which specific parameter(s) of the carbonate system drive morphological modifications. Here, we compare data on coccolith size, weight, and malformation from a set of five experiments with a large diversity of carbonate chemistry conditions. This diversity allows distinguishing the influence of individual carbonate chemistry parameters such as carbon dioxide (CO2), bicarbonate (HCO3- ), carbonate ion (CO32-), and protons (H+) on the measured parameters. Measurements of fine-scale morphological structures reveal an increase of coccolith malformation with decreasing pH suggesting that H+ is the major factor causing malformations. Coccolith distal shield area varies from about 5 to 11 µm2. Changes in size seem to be mainly induced by varying [HCO3- ] and [H+] although influence of [CO32-] cannot be entirely ruled out. Changes in coccolith weight were proportional to changes in size. Increasing CaCO3 production rates are reflected in an increase in coccolith weight and an increase of the number of coccoliths formed per unit time. The combined investigation of morphological features and coccolith production rates presented in this study may help to interpret data derived from sediment cores, where coccolith morphology is used to reconstruct calcification rates in the water column.
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This paper explores the process of creation of the netbook market by Taiwanese firms as an example of a disruptive innovation by latecomer firms. As an analytical framework, I employ the global value chain perspective to capture the dynamics of vertical inter-firm relationships that drive some firms in the chain to change the status quo of the industry. I then divide the process of the emergence of the netbook market into three consecutive stages, i.e. (1) the launch of the first-generation netbook by a Taiwanese firm named ASUSTeK, (2) the response of the two powerful platform leaders of the industry, Intel and Microsoft Intel, to ASUSTeK’s innovation, and (3) the market entry by another powerful Taiwanese firm, Acer, and explain how Taiwanese firms broke the Intel-centric market and tapped into the market-creating innovation opportunities that had been suppressed by the two powerful platform leaders. I also show that the creation of the netbook industry was an evolutionary process in which a series of responses by different industry players led to changes in the status quo of the industry.
Resumo:
In the present uncertain global context of reaching an equal social stability and steady thriving economy, power demand expected to grow and global electricity generation could nearly double from 2005 to 2030. Fossil fuels will remain a significant contribution on this energy mix up to 2050, with an expected part of around 70% of global and ca. 60% of European electricity generation. Coal will remain a key player. Hence, a direct effect on the considered CO2 emissions business-as-usual scenario is expected, forecasting three times the present CO2 concentration values up to 1,200ppm by the end of this century. Kyoto protocol was the first approach to take global responsibility onto CO2 emissions monitoring and cap targets by 2012 with reference to 1990. Some of principal CO2emitters did not ratify the reduction targets. Although USA and China spur are taking its own actions and parallel reduction measures. More efficient combustion processes comprising less fuel consuming, a significant contribution from the electricity generation sector to a CO2 dwindling concentration levels, might not be sufficient. Carbon Capture and Storage (CCS) technologies have started to gain more importance from the beginning of the decade, with research and funds coming out to drive its come in useful. After first researching projects and initial scale testing, three principal capture processes came out available today with first figures showing up to 90% CO2 removal by its standard applications in coal fired power stations. Regarding last part of CO2 reduction chain, two options could be considered worthy, reusing (EOR & EGR) and storage. The study evaluates the state of the CO2 capture technology development, availability and investment cost of the different technologies, with few operation cost analysis possible at the time. Main findings and the abatement potential for coal applications are presented. DOE, NETL, MIT, European universities and research institutions, key technology enterprises and utilities, and key technology suppliers are the main sources of this study. A vision of the technology deployment is presented.
Resumo:
We present a review of direct-drive shock ignition studies done as alternative for the Laser Mega-Joule to achieve high thermonuclear gain. One-dimensional analysis of HiPER-like Shock-ignited target designs is presented. It is shown that high gain can be achieved with shock ignition for designs which do not ignite only from the laser compression. Shock ignition is achieved for different targets of the fast ignition family which are driven by an absorbed energy between 100 kJ and 850kJ and deliver thermonuclear energies between 10-130 MJ. Shock-Ignition of Direct-Drive Double-Shell non-cryogenic target is also addressed. 2D results concerning the LMJ irradiation geometry are presented. Few systematic analyses are performed for the fuel assembly irradiation uniformity using the whole LMJ configuration or a part of the facility, and for the ignitor spike uniformity. Solutions for fuel assembly and shock ignition on LMJ using 2D calculations are presented. It is shown that high-gain shock-ignition is possible with intensity of each quad less than 1e15 W/cm2but low modes asymmetries displace the ignitor power in the spike towards higher powers.