Hadis-hadis Antropomorfisme: Analisis Terhadap Takwil Ibn Hajar Al-‘asqalânî Dalam Fath Al-bârî

: Anthropomorphism in Hadith: An Analysis of Ibn Hajar al- ‘Asqalânî\u27s Ta\u27wîl in Fath al-Bârî. In the history of Islamic theology, discussion on Quranic verses and the Prophetic traditions that deal with anthropomorphism has undergone long history starting from heated debate between literal hadith centrists with those of rationalists theologians and the Muktazilah. This essay attempts to elaborate Ibn Hajar\u27s view, as an advocate of tradition, in understanding the hadiths that describe the attributes similar to that of His creatures. In order to avoid potential error and confusion in understanding the attributes of God, Ibn Hajar utilized ta\u27wîl method and departed from his root due to socio-political condition and the prevailing theological teachings that led him to support the tenets of Asy‘ariyah. Conversely, he was very keen on safeguarding the Muslim\u27s creed from equating God\u27s attributes with His creatures

Mapping MKP-3/FOXO1 Interaction and Evaluating the Effect on Gluconeogenesis

<div><h3>Background</h3><p>MAP kinase phosphatase 3 (MKP-3) is known to attenuate the ERK signaling pathway. It has been recently demonstrated that MKP-3 is also a player in promoting hepatic glucose output in obese state by interacting and activating FOXO1. Reduction of hepatic MKP-3 expression is sufficient to reduce blood glucose levels in both diet-induced and genetically obese mice.</p> <h3>Methodology/Principal Findings</h3><p>In current study, the mechanism of MKP-3/FOXO1 interaction and the effects on transcription of gluconeogenic gene and glucose output was investigated in Fao hepatoma cells by using mutated MKP-3 and FOXO1 adenoviral constructs. The results indicate that MKP-3 phosphatase activity is not required for MKP-3/FOXO1 interaction but is essential for FOXO1 nuclear translocation and MKP-3 promoted gluconeogenesis. Compared to GFP control (1±0.38), MKP-3 increased G6Pase gene expression by 242% (3.42±0.62) while inactive MKP-3 does not change G6Pase expression (0.98±0.17). The residues 200–260 of MKP-3 and the residues 360–456 of FOXO1 are essential for mediating MKP-3/FOXO1 interaction. Interestingly, ERK phosphorylation deficient but not Akt phosphorylation deficient FOXO1 mutant lost interaction with MKP-3. Furthermore, in vivo experiments showed that Akt phosphorylation resistant FOXO1 3A mutant is sufficient to rescue the hypoglycemia caused by MKP-3 knock down in the liver of lean mice (from 141±6.78 to 209±14.64 mg/dL).</p> <h3>Conclusions/Significance</h3><p>1) Critical residues mediating MKP-3/FOXO1 interaction have been identified; 2) ERK phosphorylation deficient FOXO1 mutant is as potent as Akt phosphorylation deficient FOXO1 mutant in activating transcription of gluconeogenic genes; 3) Constitutively active FOXO1 can rescue the hypoglycemic effect caused by reduced hepatic MKP-3 expression in vivo.</p> </div

Effect of MKP-3 ERK binding domain and phosphatase activity on expression of endogenous G6Pase gene and glucose output in Fao cells.

<p><b>A.</b> Over-expression of MKP-3 WT or mutants in Fao cells and the effect on expression of endogenous G6Pase gene. <b>B.</b> Overexpression of MKP-3 WT or mutants in Fao cells and the effect on glucose output. *, P<0.05, MKP-3 wild type or mutant expressing cells versus control cells expressing GFP.</p

The Akt phosphorylation resistant FOXO1 mutant (FOXO1 3A) rescues the hypoglycemic effect caused by reduced MKP-3 expression in the liver of lean mice.

<p><b>A.</b> Body weight and glucose levels in mice injected with adenovirus expressing shGFP, shMKP-3, GFP or FOXO1 3A (n = 8 for each froup). <b>B.</b> Protein expression of MKP-3 and FOXO1 in mice as described in A (n = 4 for each group). <b>C.</b> Quantitative graphs for B. <b>D.</b> Expression of gluconeogenic genes in mice as described in A (n = 8 for each group). *, P<0.05, between groups as indicated on graphs.</p

Mapping the functional domains of FOXO1 essential for mediating the interaction between MKP-3 and FOXO1.

<p><b>A.</b> Co-immunoprecipitaion of FOXO1 WT or mutants truncated from C terminus and MKP-3 WT from Fao cells. FOXO1 WT or mutants and MKP-3 WT were co-expressed in Fao cells via adenovirus-mediated gene transfer. GFP was used as a control. <b>B.</b> Co-immunoprecipitaion of FOXO1 WT or mutants deficient in Akt or ERK phosphorylation sites and MKP-3 WT.</p

Effect of ERK binding domain and phosphatase activity on MKP-3 promoted transcription of gluconeogenic genes and FOXO1 nuclear translocation.

<p><b>A.</b> Overexpression of MKP-3 WT or mutants deficient in ERK binding domain, deficient in phosphatase activity or deficient in ERK phosphorylation sites in Fao cells and the effect on phosphorylation of ERK and FOXO1. MKP-3 WT or mutants were over-expressed in Fao cells via adenovirus-mediated gene transfer. <b>B.</b> Effect of MKP-3 wild type (WT) or mutants on transcription of PEPCK and G6Pase promoters in Fao cells. Results were presented as ratios of firefly luciferase activities (FF) versus renilla luciferase activities (RL). <b>C.</b> Effect of MKP-3 WT or mutants on nuclear translocation of FOXO1-GFP in Fao cells. Vec, vector; Luc, luciferase; veh, vehicle; Dex, dexamethasone. *, P<0.05, MKP-3 wild type or mutant expressing cells versus control cells expressing an empty vector (B) or an inactive kinase (C).</p

Mapping the functional domains of MKP-3 essential for mediating the interaction between MKP-3 and FOXO1.

<p><b>A.</b> Co-immunoprecipitation of FOXO1 WT and MKP-3 WT or mutants deficient in ERK binding domain, deficient in phosphatase activity or deficient in ERK phosphorylation sites from Fao cells. <b>B.</b> Co-immunoprecipitaion of FOXO1 WT and MKP-3 WT or mutants truncated from C terminus.</p

Pd/Phosphoramidite Thioether Complex-Catalyzed Asymmetric <i>N</i>‑Allylic Alkylation of Hydrazones with Allylic Acetates

A general and efficient Pd/phosphoramidite thioether complex-catalyzed asymmetric <i>N</i>-allylic alkylation of hydrazones with allylic acetates has been developed for the first time. The reaction allows for the preparation of various valuable <i>N</i>-substituted hydrazones with generally good yields and excellent enantioselectivities. Minor structural modification of the ligand resulted in opposite enantiomers, enabling enantiodivergent synthesis of products by the same catalytic system

Atomistic Investigation of Grain Boundary Fracture in Alumina

Grain boundary (GB) fracture is a major mechanism of material failure in polycrystalline ceramics. However, the intricate atomic arrangements of GBs have impeded our understanding of the atomistic mechanisms of these processes. In this study, we investigated the atomic-scale crack propagation behavior of an α-Al2O3 ∑13 grain boundary, using a combination of in situ transmission electron microscopy (TEM) and scanning TEM. The atomic-scale fracture path along the GB core was directly determined by the observation of the atomic structures of the fractured surfaces, which is consistent with density functional theory calculations. We found that the GB fracture can be attributed to the weaker local bonds and a smaller number of bonds along the fracture path. Our findings provide atomistic insights into the mechanisms of crack propagation along GBs, offering significant implications for GB engineering and the toughening of ceramics

Atomistic Investigation of Grain Boundary Fracture in Alumina

Grain boundary (GB) fracture is a major mechanism of material failure in polycrystalline ceramics. However, the intricate atomic arrangements of GBs have impeded our understanding of the atomistic mechanisms of these processes. In this study, we investigated the atomic-scale crack propagation behavior of an α-Al2O3 ∑13 grain boundary, using a combination of in situ transmission electron microscopy (TEM) and scanning TEM. The atomic-scale fracture path along the GB core was directly determined by the observation of the atomic structures of the fractured surfaces, which is consistent with density functional theory calculations. We found that the GB fracture can be attributed to the weaker local bonds and a smaller number of bonds along the fracture path. Our findings provide atomistic insights into the mechanisms of crack propagation along GBs, offering significant implications for GB engineering and the toughening of ceramics