52 research outputs found

    Optical phase conjugation for turbidity suppression in biological samples

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    Elastic optical scattering, the dominant light-interaction process in biological tissues, prevents tissues from being transparent. Although scattering may appear stochastic, it is in fact deterministic in nature. We show that, despite experimental imperfections, optical phase conjugation (Ξ» = 532 nm) can force a transmitted light field to retrace its trajectory through a biological target and recover the original light field. For a 0.69-mm-thick chicken breast tissue section, we can enhance point-source light return by a factor of ~5 x 10^3 and achieve a light transmission enhancement factor of 3.8 within a collection angle of 29Β°. Additionally, we find that the reconstruction's quality, measured by the width of the reconstructed point source, is independent of tissue thickness (up to a thickness of 0.69 mm). This phenomenon may be used to enhance light transmission through tissue, enable measurement of small tissue movements, and form the basis of new tissue imaging techniques

    The Primary Folding Defect and Rescue of Ξ”F508 CFTR Emerge during Translation of the Mutant Domain

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    In the vast majority of cystic fibrosis (CF) patients, deletion of residue F508 from CFTR is the cause of disease. F508 resides in the first nucleotide binding domain (NBD1) and its absence leads to CFTR misfolding and degradation. We show here that the primary folding defect arises during synthesis, as soon as NBD1 is translated. Introduction of either the I539T or G550E suppressor mutation in NBD1 partially rescues Ξ”F508 CFTR to the cell surface, but only I539T repaired Ξ”F508 NBD1. We demonstrated rescue of folding and stability of NBD1 from full-length Ξ”F508 CFTR expressed in cells to isolated purified domain. The co-translational rescue of Ξ”F508 NBD1 misfolding in CFTR by I539T advocates this domain as the most important drug target for cystic fibrosis

    Ultrathin Gold Nanowire-Functionalized Carbon Nanotubes for Hybrid Molecular Sensing

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    Carbon nanotubes (CNTs) have shown great potential as sensing component in the electrochemical, field effect transistor and optical sensors, because of their extraordinary onedimensional electronic structure, thermal conductivity, tunable and stable near-infrared emission. However, the insolubility of CNTs due to strong van der Waals interactions limits their use in the field of nanotechnology. In this study, we demonstrate that non-covalent ultrathin gold nanowires functionalized multi-walled carbon nanotube (GNW-CNT) hybrid sensing agents show highly efficient and selective immune molecular sensing in electrochemical and near-infrared photoacoustic imaging methods. A detection limit of 0.01 ng/mL for the Alpha-Fetoprotein (AFP) antigen with high selectivity is shown. The extraordinary optical absorption, thermal and electric conductivity of hybrid GNW-CNTs presented in this study could be an effective tactic to integrate imaging, sensing and treatment functionalities

    A practical guide to photoacoustic tomography in the life sciences

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    The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs

    A Chaperone Trap Contributes to the Onset of Cystic Fibrosis

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    Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of Ξ”F508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a β€˜chaperone trap’. Culturing cells at 30 C resulted in correction of Ξ”F508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that Ξ”F508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF

    Goede marktkansen voor innovatieve gastoepassingen : met fasenmodel marktpotentieel bepalen

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    Innovatieve gastoepassingen hebben de belangstelling van Gasunie. Niet alleen om de gasafzet te verhogen, maar ook om de energiebedrijven te ondersteunen bij het ontwikkelen van commerciele activiteiten en om verantwoord energieverbruik te stimuleren. Gasunie ondersteunt de ontwikkeling en het gebruik van gastoepassingen vaak actief vanuit de strategische marketing activiteiten van Gasunie, onder meer in het Marketingplan Openbare Gasvoorziening (MOG).

    Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity

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    Background and aims - Diets high in monounsaturated fatty acids (MUFA) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids. Besides being high in MUFA, a Mediterranean diet also contains abundant plant foods, moderate wine and low amounts of meat and dairy products, which may also play a role. We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids (SFA) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids. Methods and results - A randomized parallel controlled-feeding trial was performed, in 60 non-diabetics (40–65 y) with mild abdominal obesity. After a two week run-in diet high in SFA (19 energy-%), subjects were allocated to a high MUFA-diet (20 energy-%), a Mediterranean diet (MUFA 21 energy-%), or the high SFA-diet, for eight weeks. The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations. The high MUFA-diet reduced total cholesterol (-0.41 mmol/L, 95% CI -0.74, -0.09) and LDL-cholesterol (-0.38 mmol/L, 95% CI -0.65, -0.11) compared with the high SFA-diet, but not triglyceride concentrations. The Mediterranean diet increased HDL-cholesterol concentrations (+0.09 mmol/L, 95% CI 0.0, 0.18) and reduced the ratio of total cholesterol/HDL-cholesterol (-0.39, 95% CI -0.62, -0.16) compared with the high MUFA-diet. Conclusion - Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity, but improved serum lipids. The Mediterranean diet was most effective, it reduced total and LDL-cholesterol, and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio

    Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity

    No full text
    Background and aims - Diets high in monounsaturated fatty acids (MUFA) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids. Besides being high in MUFA, a Mediterranean diet also contains abundant plant foods, moderate wine and low amounts of meat and dairy products, which may also play a role. We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids (SFA) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids. Methods and results - A randomized parallel controlled-feeding trial was performed, in 60 non-diabetics (40–65 y) with mild abdominal obesity. After a two week run-in diet high in SFA (19 energy-%), subjects were allocated to a high MUFA-diet (20 energy-%), a Mediterranean diet (MUFA 21 energy-%), or the high SFA-diet, for eight weeks. The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations. The high MUFA-diet reduced total cholesterol (-0.41 mmol/L, 95% CI -0.74, -0.09) and LDL-cholesterol (-0.38 mmol/L, 95% CI -0.65, -0.11) compared with the high SFA-diet, but not triglyceride concentrations. The Mediterranean diet increased HDL-cholesterol concentrations (+0.09 mmol/L, 95% CI 0.0, 0.18) and reduced the ratio of total cholesterol/HDL-cholesterol (-0.39, 95% CI -0.62, -0.16) compared with the high MUFA-diet. Conclusion - Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity, but improved serum lipids. The Mediterranean diet was most effective, it reduced total and LDL-cholesterol, and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio
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