Allosteric Regulation of Pyruvate Carboxylase

Pyruvate carboxylase (PC; E.C.6.4.1.1) is a multifunctional, biotin-dependent enzyme that catalyzes the MgATP-dependent carboxylation of pyruvate to oxaloacetate. The overall reaction is accomplished by the coupling of two half reactions occurring at two spatially distinct catalytic domains by the translocation of a carrier domain, resulting in a net transfer of CO2 from bicarbonate to pyruvate. PC activity is regulated by multiple allosteric effectors with acetyl CoA serving as an activator in most species and L-aspartate serving as an inhibitor for microbial PC. The kinetic characterization of PC from different species have revealed that PC homologs are subject to divergent degrees of allosteric regulation, yet the mechanism controlling the allosteric response still remains unknown. Rhizobium etli (RePC) is allosterically activated by acetyl CoA, while Aspergillus nidulans (AnPC) is unique in not being activated by acetyl CoA. The divergent regulatory properties of these two PC homologs were investigated in order to uncover the fundamental mechanism underlying the allosteric regulation of pyruvate carboxylase. The lack of sensitivity to acetyl CoA activation was determined to be an intrinsic property of the BC domain rather than a consequence of different acetyl CoA binding sites. Further characterization of AnPC compared to RePC revealed that AnPC is a highly stable tetramer that remains in a permanently activated state. A more ordered transition state and coupled half reactions contribute to its high intrinsic catalytic rate as well as the insensitivity to the activation by acetyl CoA. Investigations on the translocation of the carrier domain revealed that multiple translocation pathways are adopted by the carrier domain in PC during catalysis. Interestingly, an intermolecular translocation pathway was promoted upon binding with acetyl CoA in RePC, which likely contributes to the enhanced coupling efficiency as well as the elevated catalytic rate observed in RePC. Finally, studies on the allosteric inhibition of PC by L-aspartate revealed that the antagonistic effects of acetyl CoA and L-aspartate to the catalysis of PC result from their competitive binding at a partially overlapping binding site. Collectively, these studies offer new insights into the mechanism of allosteric regulation in pyruvate carboxylase and provide an example of how divergent intrinsic properties in homologous enzymes can give rise to their unique regulatory properties

Young Engels Is Still Engels: A Response to Terrell Carver

Terrel Carver assumes that existing biographies of Engels unfairly seek to explain his ideas in relation to Marx and seek to reconstruct the life journey, especially the ideological journey, of young Engels. He proposes two arguments: first, Engels\u27 ideological growth had no direct purpose or direction and was full of uncertainties; but also, second, that the young Engels\u27 theoretical achievements have been unduly underestimated as they were much more profound than Marx\u27s, such that Marx was the main beneficiary of their initial meeting. One problem with Carver’s argument is that his new insights are often not that new at all. His anti-teleological Engels is a liberal, but this is a more-or-less static form of liberalism that seems innocent of any immanent mechanism through which Engels’s trajectory toward revolutionary socialism might be understood. “Engels vs. Marx” is a trite trope. The proposition of “Engels vs. Marx” functions to deny the theory and practice of Marxist revolutionaries and politicians after Engels. This is something that the left academia should be vigilant about

Allosteric Regulation Alters Carrier Domain Translocation in Pyruvate Carboxylase

Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. The reaction occurs in two separate catalytic domains, coupled by the long-range translocation of a biotinylated carrier domain (BCCP). Here, we use a series of hybrid PC enzymes to examine multiple BCCP translocation pathways in PC. These studies reveal that the BCCP domain of PC adopts a wide range of translocation pathways during catalysis. Furthermore, the allosteric activator, acetyl CoA, promotes one specific intermolecular carrier domain translocation pathway. These results provide a basis for the ordered thermodynamic state and the enhanced carboxyl group transfer efficiency in the presence of acetyl CoA, and reveal that the allosteric effector regulates enzyme activity by altering carrier domain movement. Given the similarities with enzymes involved in the modular synthesis of natural products, the allosteric regulation of carrier domain movements in PC is likely to be broadly applicable to multiple important enzyme systems

A Natural Language Processing Approach to Analyzing Consultation Visits for Treatment Decision Making for Localized Prostate Cancer

This quantitative study investigates the information seeking and giving behaviors of doctors, prostate cancer patients and their family members during consultation visits. The dataset was a transcript of audio-recordings of real-time treatment consultations collected from 171 consultation visits in a clinical trial. For text analysis purposes, a question mark in a transcript sentence was used to signal the information seeking behavior while a period was used to signal information giving behavior. Two counting methods were adopted to investigate the effect of a decision aid intervention that was created to facilitate the prostate cancer patient consultation. Data process, cleaning and analysis were performed by Python, which shows the decision aid intervention promoted the patient’s information seeking and giving behavior during the consultations. Topic analysis of specific target population showed different communication styles from Caucasian and African America population. What’s more, the results contribute to the decision aid for patients and training on communications in the clinical visits.Master of Science in Information Scienc

Study on the Effect of Cuisine Tourism Resource on Tourists’ Willingness to Visit

This article aims at examining if tourists’ evaluation of cuisine tourism resource has a positive effect on their willingness to visit (WTV) the destination (H1). In Study 1, the content analysis of travelogues of 60 Chinese major tourist cities shows that the scenic spots have a significant effect on WTV, while the effect of cuisine tourism resource on WTV is not supported. Moreover, the tourist city Chengdu with both abundant scenic spots and cuisine resources is chosen for further research of how cuisine resources influence tourist’ decisions. In term of 276 questionnaires (Study 2) and 30 interviewee (Study 3), the results show that the impact of the cuisine resource on WTV is moderated by the tourists’ evaluation on the scenic spots. Only when tourists have a high evaluation on scenic spots, the cuisine resource plays a positive impact on WTV, showing the auxiliary attraction of cuisine resource to tourists

Exploring the inheritance and historical evolution of cultural values from the perspective of folk songs and chorus

Folk songs and choirs are both ways of presenting musical works, and the participating groups of these two forms of music are more inclined towards grassroots people, recording the characteristics of people's lives and times. It carries the inheritance and historical evolution of cultural values in its development process. This article will analyze the development history and presentation methods of folk songs and choirs, as well as their recording patterns of culture and history. It will also explore the cultural value inheritance and historical evolution reflected in the growth of works from the perspectives of folk songs and choirs

Experimental Investigation of Flow Control Using Blade End Slots in a Highly Loaded Compressor Cascade

International audienceA detailed experimental investigation is conducted to suppress three-dimensional (3D) corner separation by a proposed passive control method using blade end slots in a highly loaded high-speed compressor cascade. Experiments are carried out under a wide range of incidence angles at Ma=0.59 using blades with and without blade end slots, respectively. Based on the experimental results, extensive comparisons show that the proposed method using blade end slots can efficiently suppress the 3D corner separation and broaden the effective operating range in the highly loaded high-speed compressor cascade. The total pressure loss is significantly reduced under most conditions. The reduction of total pressure loss in the measurement plane is as high as 18.4%, 20.6%, 24.3% and 39.4% at the incidence angle of-1.69˚, 0˚, 2˚ and 4˚, respectively. Furthermore, spanwise distributions of the pitch-averaged total pressure loss and deviation angle as well as the 3D flow field structures are analyzed to reveal the flow control mechanisms using blade end slots. The blade end slots can generate self-adaptive high momentum jet flow through the pressure difference from blade pressure and suction surface. These jet flows from the blade end slots effect downstream along the blade suction surface and significantly increase the flow momentum in the corner region. The main secondary vortex structures are suppressed by the high momentum jet flow; the 3D corner separation is reduced, and the two-dimesionality in the mid-span region is enhanced