45,103 research outputs found
Biologically targeted probes for Zn2+: a diversity oriented modular “click-SNAr-click” approach
Full text linkWe describe a one-pot strategy for the high yielding, operationally simple synthesis of fluorescent probes for Zn2+ that bear biological targeting groups and exemplify the utility of our method through the preparation of a small library of sensors. Investigation of the fluorescence behaviour of our library revealed that although all behaved as expected in MeCN, under biologically relevant conditions in HEPES buffer, a plasma membrane targeting sensor displayed a dramatic switch on response to excess Zn2+ as a result of aggregation phenomena. Excitingly, in cellulo studies in mouse pancreatic islets demonstrated that this readily available sensor was indeed localised to the exterior of the plasma membrane and clearly responded to the Zn2+ co-released when the pancreatic beta cells were stimulated to release insulin. Conversely, sensors that target intracellular compartments were unaffected. These results demonstrate that this sensor has the potential to allow the real time study of insulin release from living cells and exemplifies the utility of our simple synthetic approac
N. K. Rutter (éd.) avec des contributions de A.M. Burnett, М.Н. Crawford, A.E.M. Johnston et M. Jessop Price|, Historia Numorum Italy.
No full textAmandry Michel. N. K. Rutter (éd.) avec des contributions de A.M. Burnett, М.Н. Crawford, A.E.M. Johnston et M. Jessop Price|, Historia Numorum Italy.. In: Revue numismatique, 6e série - Tome 160, année 2004 pp. 376-377
Continuous Structured Population Models for Daphnia Magna
No full textIndividual-level data for food-restriction experiments for Daphnia magna in the paper:
Rutter, E. M., Banks, H. T., LeBlanc, G.A., and Flores, K. B. Continuous Structured Population Models of Daphnia magna. Bulletin of Mathematical Biology, 2017, 79(11):2627-2648. DOI: DOI:10.1007/s11538-017-0344-
Measurement of the ratio of branching fractions B(B0→K∗0γ )/B(B0s→φγ ) and the directCP asymmetry inB 0→K∗0γ
Full text linkThe ratio of branching fractions of the radiative B decays B0→K⁎0γ and B0s→ϕγ has been measured using an integrated luminosity of 1.0 fb−1 of pp collision data collected by the LHCb experiment at a centre-of-mass energy of s√=7TeV. The value obtained is
B(B0→K⁎0γ)B(B0s→ϕγ)=1.23±0.06(stat.)±0.04(syst.)±0.10(fs/fd),
where the first uncertainty is statistical, the second is the experimental systematic uncertainty and the third is associated with the ratio of fragmentation fractions fs/fd. Using the world average value for B(B0→K⁎0γ), the branching fraction B(B0s→ϕγ) is measured to be (3.5±0.4)×10−5.
The direct CP asymmetry in B0→K⁎0γ decays has also been measured with the same data and found to be
ACP(B0→K⁎0γ)=(0.8±1.7(stat.)±0.9(syst.))%.
Both measurements are the most precise to date and are in agreement with the previous experimental results and theoretical expectations
Glucose generates sub-plasma membrane ATP microdomains in single islet beta-cells. Potential role for strategically located mitochondria.
No full textIncreases in the concentration of free ATP within the islet beta-cell may couple elevations in blood glucose to insulin release by closing ATP-sensitive K+ (KATP) channels and activating Ca2+ influx. Here, we use recombinant targeted luciferases and photon counting imaging to monitor changes in free [ATP] in subdomains of single living MIN6 and primary beta-cells. Resting [ATP] in the cytosol ([ATP]c), in the mitochondrial matrix ([ATP]m), and beneath the plasma membrane ([ATP]pm) were similar ( approximately 1 mM). Elevations in extracellular glucose concentration (3-30 mM) increased free [ATP] in each domain with distinct kinetics. Thus, sustained increases in [ATP]m and [ATP]pm were observed, but only a transient increase in [ATP]c. However, detectable increases in [ATP]c and [ATP]pm, but not [ATP]m, required extracellular Ca2+. Enhancement of glucose-induced Ca2+ influx with high [K+] had little effect on the apparent [ATP]c and [ATP]m increases but augmented the [ATP]pm increase. Underlying these changes, glucose increased the mitochondrial proton motive force, an effect mimicked by high [K+]. These data support a model in which glucose increases [ATP]m both through enhanced substrate supply and by progressive Ca2+-dependent activation of mitochondrial enzymes. This may then lead to a privileged elevation of [ATP]pm, which may be essential for the sustained closure of KATP channels. Luciferase imaging would appear to be a useful new tool for dynamic in vivo imaging of free ATP concentration
How Cells Choose To Create Energy
No full textTo supply their energy needs, cells typically choose between utilizing glucose in the cytoplasm (aerobic glycolysis and lactic acid fermentation) or "burning" pyruvate in the mitochondria (mitochondrial carbohydrate oxidation). Although this is arguably the most fundamental metabolic decision that cells must make, prior to 2012 it was not clear how cells import pyruvate into mitochondria to fuel ATP production. That year, Rutter, Thummel and colleagues identified the heterodimeric MPC1/MPC2 complex as the mitochondrial pyruvate carrier. Their paper also identified and explained the severe metabolic defects found in families with mpc1 gene mutations. Rutter and collaborators have subsequently shown that the choice of whether or not to import pyruvate has far-reaching medical implications because stem cells and most cancer cells are glycolytic (the "Warburg Effect"). They showed that this is often because cells down-regulate MPC expression, and that MPC re-expression reverses the Warburg Effect, impedes tumor growth, and drives cell differentiation. These discoveries have revolutionized our understanding of the role of metabolic decisions in determining cell state and fate
∑_(l+m=k,l,m≥0) ((α+l-1)¦l) ((β+m-1)¦m)=((α+β+k-1)¦k) and its application to negative binomial distribution
Full text linkWe prove here the following equation: ∑_(l+m=k,l,m≥0) ((α+l-1)¦l) ((β+m-1)¦m)=((α+β+k-1)¦k) and give its application to prove the reproductive property of the negative binomial distribution.
These finite sum equation involving binomial coefficients and proof of the reproductive property are not known as far as the author knows.論文(Article)departmental bulletin pape
MiR-184 expression is regulated by AMPK in pancreatic islets
Full text linkAMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets
Intracellular ATP-sensitive K+ channels in mouse pancreatic beta cells: Against a role in organelle cation homeostasis
No full textAims/hypothesis: ATP-sensitive K+ (KATP) channels located on the beta cell plasma membrane play a critical role in regulating insulin secretion and are targets for the sulfonylurea class of antihyperglycaemic drugs. Recent reports suggest that these channels may also reside on insulin-containing dense-core vesicles and mitochondria. The aim of this study was to explore these possibilities and to test the hypothesis that vesicle-resident channels play a role in the control of organellar Ca 2+ concentration or pH. Methods: To quantify the subcellular distribution of the pore-forming subunit Kir6.2 and the sulfonylurea binding subunit SUR1 in isolated mouse islets and clonal pancreatic MIN6 beta cells, we used four complementary techniques: immunoelectron microscopy, density gradient fractionation, vesicle immunopurification and fluorescence-activated vesicle isolation. Intravesicular and mitochondrial concentrations of free Ca 2+ were measured in intact or digitonin-permeabilised MIN6 cells using recombinant, targeted aequorins, and intravesicular pH was measured with the recombinant fluorescent probe pHluorin. Results: SUR1 and Kir6.2 immunoreactivity were concentrated on dense-core vesicles and on vesicles plus the endoplasmic reticulum/Golgi network, respectively, in both islets and MIN6 cells. Reactivity to neither subunit was detected on mitochondria. Glibenclamide, tolbutamide and diazoxide all failed to affect Ca2+ uptake into mitochondria, and KATP channel regulators had no significant effect on intravesicular free Ca2+ concentrations or vesicular pH. Conclusions/Interpretation: A significant proportion of Kir6.2 and SUR1 subunits reside on insulin-secretory vesicles and the distal secretory pathway in mouse beta cells but do not influence intravesicular ion homeostasis. We propose that dense-core vesicles may serve instead as sorting stations for the delivery of channels to the plasma membrane. © Springer-Verlag 2006
On Turn-Regular Orthogonal Representations
No full textAn interesting class of orthogonal representations consists of the so-called turn-regular ones, i.e., those that do not contain any pair of reflex corners that “point to each other” inside a face. For such a representation H it is possible to compute in linear time a minimum-area drawing, i.e., a drawing of minimum area over all possible assignments of vertex and bend coordinates of H. In contrast, finding a minimum-area drawing of H is NP-hard if H is non-turn-regular. This scenario naturally motivates the study of which graphs admit turn-regular orthogonal representations. In this paper we identify notable classes of biconnected planar graphs that always admit such repre-sentations, which can be computed in linear time. We also describe a linear-time testing algorithm for trees and provide a polynomial-time algorithm that tests whether a bi-connected plane graph with “small” faces has a turn-regular orthogonal representation without bends
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