8,126 research outputs found

    In situ chemichromic studies of interactions between a lutetium bis-octaalkyl-substituted phthalocyanine and selected biological cofactors

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    This article is available open access through the publisher’s website at the link below. Copyright @ 2011 The Royal Society.Spin-coated films, approximately 100 nm thick, of a newly synthesized bis[octakis(octyl)phthalocyaninato] lutetium(III) complex on ultrasonically cleaned glass substrates exhibit pronounced chemichromic behaviour with potential application in healthcare. In situ kinetic optical absorption spectroscopic measurements show that the phthalocyanine Q-band is red shifted by 60 nm upon oxidation arising from exposure to bromine vapour. Recovery to the original state is achieved by the treatment of the oxidized films with nicotinamide adenine dinucleotide and l-ascorbic acid (vitamin C) in an aqueous solution containing 1.5 M lithium perchlorate. The neutralization process is found to be governed by first-order kinetics. The linear increase of the reduction rate with increasing concentration of cofactors provides a basis for calibration of analyte concentrations ranging from 3.5 mM down to 0.03 mM.Air Force Office of Scientific Research, Air Force Material Command, USAF and the Leverhulme Trust

    Microtubules regulate cardiomyocyte transversal Young's modulus.

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    The field of cardiomyocyte mechanobiology is gaining significant attention, due to accumulating evidence concerning the significant role of cellular mechanical effects on the integrated function of the heart. To date, the protein titin has been demonstrated as a major contributor to the cardiomyocytes Young's modulus (YM). The microtubular network represents another potential regulator of cardiac mechanics. However, the contribution of microtubules (MTs) to the membrane YM is still understudied and has not been interrogated in the context of myocardial infarction (MI) or mechanical loading and unloading. Using nanoscale mechanoscanning ion conductance microscopy, we demonstrate that MTs contribute to cardiomyocyte transverse YM in healthy and pathological states with different mechanical loading. Specifically, we show that posttranslational modifications of MTs have differing effects on cardiomyocyte YM: Acetylation provides flexibility, whereas detyrosination imparts rigidity. Further studies demonstrate that there is no correlation between the total protein amount of acetylated and detyrosinated MT. Yet, in the polymerized-only populations, an increased level of acetylation results in a decline of detyrosinated MTs in an MI model

    Metabolic rate and hypoxia tolerance in Girardinichthys multiradiatus (Pisces: Goodeidae), an endemic fish at high altitude in tropical Mexico

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    Artículo científico JCR Q1The darkedged splitfin (Amarillo fish), Girardinichthys multiradiatus is a vulnerable endemic fish species inhabiting central Mexico's high altitude Upper Lerma Basin, where aquatic hypoxia is exacerbated by low barometric pressures (lower PO2s), large aquatic oxygen changes, poor aquatic systems management and urban, agricultural and industrial pollution. The respiratory physiology of G. multiradiatus under such challenging conditions is unknown - therefore the main goal of the present study was to determine metabolic rates and hypoxia tolerance to elucidate possible physiological adaptations allowing this fish to survive high altitude and increasingly eutrophic conditions. Fish came from two artificial reservoirs – San Elías and Ex Hacienda - considered refuges for this species. Both reservoirs showed high dial PO2 variation, with hypoxic conditions before midday and after 20:00 h, ~4 h of normoxia (15 kPa) from 16:00–20:00, and ~4 h of hyperoxia (16–33 kPa) from 12:00–16:00. Standard metabolic rate at 20 ± 0.5 °C of larvae from Ex Hacienda was significantly higher than those from San Elías, but these differences disappeared in juveniles and adults. Metabolic rate at 20 ± 0.5 °C for adults was 9.8 ± 0.1 SEM μmol O2/g/h. The metabolic scaling exponent for adults was 0.58 for San Elías fish and 0.83 for Ex Hacienda fish, indicating possible ecological effects on this variable. Post-larval fish in Ex Hacienda and all stages in San Elias site showed considerable hypoxia tolerance, with PCrit mean values ranging from 1.9–3.1 kPa, lower than those of many tropical fish at comparable temperatures. Collectively, these data indicate that G. multiradiatus is well adapted for the hypoxia associated with their high-altitude habitat.CONACyT PRODEP-SEP UAEMé

    Short-term angiotensin II treatment regulates cardiac nanomechanics via microtubule modifications.

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    Mechanical properties of single myocytes contribute to the whole heart performance, but the measurement of mechanics in living cells at high resolution with minimal force interaction remains challenging. Angiotensin II (AngII) is a peptide hormone that regulates a number of physiological functions, including heart performance. It has also been shown to contribute to cell mechanics by inducing cell stiffening. Using non-contact high-resolution Scanning Ion Conductance Microscopy (SICM), we determine simultaneously cell topography and membrane transverse Young's modulus (YM) by a constant pressure application through a nanopipette. While applying pressure, the vertical position is recorded and a deformation map is generated from which YM can be calculated and corrected for the uneven geometry. High resolution of this method also allows studying specific membrane subdomains, such as Z-grooves and crests. We found that short-term AngII treatment reduces the transversal YM in isolated adult rat cardiomyocytes acting via an AT1 receptor. Blocking either a TGF-β1 receptor or Rho kinase abolishes this effect. Analysis of the cytoskeleton showed that AngII depletes microtubules by decreasing long-lived detyrosinated and acetylated microtubule populations. Interestingly, in the failing cardiomyocytes, which are stiffer than controls, the short-term AngII treatment also reduces the YM, thus normalizing the mechanical state of cells. This suggests that the short-term softening effect of AngII on cardiac cells is opposite to the well-characterized long-term hypertrophic effect. In conclusion, we generate a precise nanoscale indication map of location-specific transverse cortical YM within the cell and this can substantially advance our understanding of cellular mechanics in a physiological environment, for example in isolated cardiac myocytes

    Early characterization of the severity and transmissibility of pandemic influenza using clinical episode data from multiple populations

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    The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133-0.150 and R0, 1.09-2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics
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