scholarly journals 5) Novel Insight into Physiological and Pathophysiological Roles of Adipocytes -Elucidation of Adiponectin Receptors AdipoRs Action Mechanisms and Clinical Application-

2016 ◽  
Vol 105 (9) ◽  
pp. 1746-1752
Author(s):  
Toshimasa Yamauchi ◽  
Takashi Kadowaki
2017 ◽  
Vol 15 (19) ◽  
Author(s):  
Marek Volt

Artiklis käsitlen Lev Tolstoi kunstiteooria retseptsiooni anglo-ameerika esteetikas. Esiteks formuleerin Tolstoi kunstidefinitsiooni ja selle põhimõistete kanoonilise tõlgenduse. Seejärel analüüsin määratlust ekstensionaalse adekvaatsuse alusel, keskendudes nii tavapäraste kui võimalike uute etteheidete paikapidavuse uurimisele. Kolmandaks püstitan küsimuse, kas Tolstoi kunstidefinitsiooni kriitika ekstensionaalse adekvaatsuse alusel on üldse õigustatud. Väidan, et kuigi senistel Tolstoi meta-esteetilise rehabiliteerimise katsetel esineb puuduseid, paljastab Tolstoi kunstiteooria immanentne kriitika – teooria vaagimine eeldustelt, millelt see kritiseerib oponeerivaid teooriaid –, et ekstensionaalsest adekvaatsusest lähtuv kriitika on õigustatud. My article discusses Tolstoy’s theory of art in the context of Anglo-American aesthetics. Although Tolstoy’s What is Art touches upon a very wide spectrum of subjects (the place of art in the world, justification of sacrifices made for completing art works, criticism of previous theories of aesthetics, especially of the theory of beauty, defining of art as the expression of feelings, judging of art as such based on the religious knowledge of the era, action mechanisms of beauty/pleasure-centred art, consequences, conditions of the value of art, the relations between art and science, etc.), it has mainly been examined from the aspects of judging and defining of art.The article focuses on Tolstoy’s definition of art and consists of three notional parts. First, I present the canonical formulation of Tolstoy’s definition of art – something is a work of art if and only if the person, who lives through the feeling(s), causes by external signs that the recipients live through the same feelings. I also present the canonical interpretation of its main concepts – the conditions for creation, transmitting and reception.Second, I have an analytical insight into the criticism of the canonical treatment, displaying and commenting on, but also responding and complementing the presented arguments. The extensional adequacy-based analysis of Tolstoy’s definition of art shows that although it is possible to eliminate some of the typical criticisms, none of the three necessary conditions was necessary by itself, nor were all three of them sufficient when taken together.As Tolstoy’s definition of art has sometimes earned quite serious criticism, then, as my third point, I also examine some possibilities for rehabilitating Tolstoy’s theory of art: whether and in what sense can the extensional adequacy-based analysis of Tolstoy’s definition of art be justified at all? So far, the attempts of meta-aesthetic rehabilitation of Tolstoy (e.g., Mounce centrism) have not achieved the expected result. Furthermore, the immanent criticism of Tolstoy’s theory of art (criticism of the theory, based on the prerequisites it uses to criticize its opposing theories) reveals that the extensional adequacy-based criticism of Tolstoy’s definition of art is justified, but it is not necessarily the only yardstick for the theory.


2018 ◽  
Author(s):  
Jae Kyo Yi ◽  
Ruijuan Xu ◽  
Lina M. Obeid ◽  
Yusuf A. Hannun ◽  
Michael V. Airola ◽  
...  

ABSTRACTHuman alkaline ceramidase 3 (ACER3) is one of three alkaline ceramidases (ACERs) that catalyze the conversion of ceramide to sphingosine. ACERs are the members of the CREST superfamily of integral-membrane lipid hydrolases, including the adiponectin receptors which play roles in energy metabolism. All CREST members conserve a set of three Histidine, one Aspartate, and one Serine residue. However, the structural and catalytic roles for these residues are unclear. Here, we use ACER3 as a prototype enzyme to gain insight into this unique class of enzymes. Recombinant ACER3 was expressed in yeast cells that lack endogenous ceramidase activity, and microsomes were used for biochemical characterization. Six point mutantions of the conserved CREST motif were developed that are predicted to form a Zn-dependent active site based on homology with the human adiponectin receptors, whose crystal structures were recently determined. Five mutations completely lost their activity, except for S77A, which showed a 600-fold decrease compared with the wild-type enzyme. The activity of S77C mutation was pH sensitive, with neutral pH partially recovering ACER3 activity. This suggested a role for S77 in stabilizing the oxyanion of the transition state and differs from the proposed role in Zinc coordination for the adiponectin receptors (Vasiliauskaité-Brooks et. al., Nature, 2017). Together, these data suggest ACER3 is a Zn2+-dependent amidase that uses a catalytic mechanism for ceramide hydrolysis that is similar to other soluble Zn-based amidases. Consistent with this mechanism, ACER3 was specifically inhibited by trichostatin A, an HDAC inhibitor, which is a strong chelator of Zinc.


2014 ◽  
Vol 13 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Prashant Chittiboina ◽  
John D. Heiss ◽  
Katherine E. Warren ◽  
Russell R. Lonser

Object Coinfused surrogate imaging tracers can provide direct insight into the properties of convection-enhanced delivery (CED) in the nervous system. To better understand the distributive properties of CED in a clinical circumstance, the authors analyzed the imaging findings in pediatric diffuse intrinsic pontine glioma (DIPG) patients undergoing coinfusion of Gd-DTPA and interleukin-13–Pseudomonas exotoxin (IL13-PE). Methods Consecutive patients undergoing CED (maximal rates of 5 or 10 μl/minute) of Gd-DTPA (1 or 5 mM) and IL13-PE (0.125 μg/ml or 0.25 μg/ml) for DIPG were included. Real-time MRI was performed during infusions, and imaging results were analyzed. Results Four patients (2 males, 2 females; mean age at initial infusion 13.0 ± 5.3 years; range 5–17 years) underwent 5 infusions into DIPGs. Brainstem infusions were clearly identified on T1-weighted MR images at 1-mM (1 infusion) and 5-mM (4 infusions) coinfused Gd-DTPA concentrations. While the volume of distribution (Vd) increased progressively with volume of infusion (Vi) (mean volume 2.5 ± 0.9 ml; range 1.1–3.7 ml), final Vd:Vi ratios were significantly reduced with lower Gd-DTPA concentration (Vd:Vi for 1 mM of 1.6 compared with a mean Vd:Vi ratio for 5 mM of 3.3 ± 1.0) (p = 0.04). Similarly, anatomical distribution patterns were affected by preferential flow along parallel axial fiber tracts, into prior infusion cannula tracts and intraparenchymal air pockets, and leak back around the infusion cannula at the highest rate of infusion. Conclusions Magnetic resonance imaging of a coinfused Gd-DTPA surrogate tracer provided direct insight into the properties of CED in a clinical application. While clinically relevant Vds can be achieved by convective delivery, specific tissue properties can affect distribution volume and pattern, including Gd-DTPA concentration, preferential flow patterns, and infusion rate. Understanding of these properties of CED can enhance its clinical application. Part of clinical trial no. NCT00880061 (ClinicalTrials.gov).


Mycoses ◽  
2020 ◽  
Vol 63 (9) ◽  
pp. 979-992 ◽  
Author(s):  
Pedro F. N. Souza ◽  
Patrícia G. Lima ◽  
Cleverson D. T. Freitas ◽  
Daniele O. B. Sousa ◽  
Nilton A. S. Neto ◽  
...  

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