The structure and function of human brain hexokinase

An ATP binding site model for human brain hexokinase was established based on the similarity of the ATP-binding domains among actin, heat shock protein, glycerol kinase and brain hexokinase. Site directed mutagenesis was performed on the residues in the putative ATP-binding site in order to substantiate or refute the proposed model. The k cat values decreased 1000- and 200-fold for the Asp532Lys and Asp532Glu mutants, 114- and 12-fold for the Arg539Ile and Arg539Lys mutants, 2000- and 2-fold for the Thr680Val and Thr680Ser mutants, respectively. It is suggested that these residues are important for catalysis by either keeping the [gamma]-phosphoryl group of ATP in the correct orientation for catalysis or stabilizing the transition state of the reaction. The mutant Gly534Ala exhibited a 4000-fold decrease in its k catvalue. It appears that the small side chain of Gly534 is important to provide space for ATP binding in the correct orientation. The Gly679Ala mutant did not show any significant change in kinetic parameters, whereas the Gly679Ile mutant was overexpressed as an insoluble protein. Thus, Gly679 is probably responsible for correct folding of the enzyme;Crystals for human brain hexokinase complexed with inorganic phosphate, glucose, or glucose-6-phosphate were obtained. The ternary complex of human brain hexokinase-ATP-glucose was also crystallized. X-ray diffraction data has been collected. The solution of the three dimensional structure is currently being carried out;Minihexokinase was overexpressed in Escherichia coli BL21(DE3) strain and purified to homogeneity. Minihexokinase lost its ability to ameliorate inhibition of glucose-6-P-inhibited mini-hexokinase in the presence of phosphate (Pi). These findings suggest that the Pi site either resides in the N-terminal half of hexokinase or requires the N-terminal portion of the enzyme;The purification procedure for human brain hexokinase was improved, producing 10-fold more protein in half the time

Reminders of Mortality Alter Pain-Evoked Potentials in a Chinese Sample

Pain is of evolutionary importance to human survival. However, the perception of pain could be changed when death-related thoughts are accessible. Although the influence of mortality salience (MS) on pain processing has been investigated in Westerners recently, it is unclear whether this effect is constrained by specific culture context since humans may employ cultural worldviews to defend the existence problem. The current study tested whether and how MS affected pain processing in a Chinese male sample. We primed participants with sentences indicating MS or negative affect (NA) on either of two days. Both before and after the priming, event-related potentials (ERPs) elicited by painful and non-painful electrical stimulations were recorded. Results showed that pain-evoked potentials were identified as an early negative complex N60-P90-N130 and a late positivity P260. Pain-evoked N130 after MS priming was larger than that after NA priming. Meanwhile, pain-evoked P260 decreased after MS priming but not after NA priming. These findings indicate that reminders of mortality affect both early sensory and late cognitive neural responses related to physical pain. Although previous studies reporting an increased effect of MS on perceived pain intensity in Westerners, we found an unchanged or possibly reduced effect in Chinese. Thus, the current work provides insight into a culture-sensitive perspective on how pain processing would be modulated when existential problem occurs

Leveraging Data-driven Approaches to Explore the Effect of Various Disaster Policies on Post-earthquake Household Relocation Decision-making

Earthquake events can cause affected households to relocate. Post-earthquake relocation disrupts displaced households’ social ties as well as their access to affordable services. Simulation models that capture post-earthquake relocation decision-making can be useful tools for supporting the development of related disaster risk reduction policies that aim at mitigating disaster-induced relocation. Yet, existing versions of these models focus particularly on housing-related factors (e.g., housing repair costs), which are not the sole driver of post-earthquake relocation. In this paper, we integrate data-driven approaches and local perspectives into an existing simulation-based framework to holistically capture various context-specific factors perceived as being important to household relocation decision-making. The enhanced framework is used to quantitatively assess the effectiveness of various disaster risk reduction policies - both ‘soft’ (e.g., post-earthquake livelihood assistance funds) and ‘hard’ (e.g., upgrading existing infrastructure facilities to higher building codes) - in reducing post-earthquake household relocation, with an explicit focus on low-income households. We demonstrate it using a possible future (50-year) projection of “Tomorrowville”, a synthetic expanding urban extent that imitates a Global South setting. Our analyses suggest that livelihood assistance funds are more successful and pro-poor when it comes to mitigating positive post-earthquake relocation decision-making than hard policies focused on strengthening buildings (at least in the context of the examined case study)

A Contradiction to the Law of Energy Conservation by Waves Interference in Symmetric/Asymmetric mode

It can be agreed that the linear superposition and energy conservation are two independent physics laws in general. The former allows the energy to be re-distributed over space and the latter restricts the energy in the total amount. However, Levine shows the contradiction of the two laws mentioned above by creating a cleaver model that demonstrates the energy "doubling"- and "missing" phenomenon with the constrictive- and destructive interference at every point of whole space, respectively. While, he presented a wrong explanation by using one of the radiating sources to compare with an isolated source by the compensation of the impedance, where the mistake is simply analyzed in this paper. By setting up a spatial symmetric- and asymmetric-mode, we work upon Poynting theorem from the sources to the waves with the considerations of the superposition. The theoretical results reveal the invalidity of the energy conservation. Moreover, the experiments performed in the microwave anechoic chamber confirm the theoretical conclusion

Leveraging data-driven approaches to explore the effect of various disaster policies on post-earthquake household relocation decision-making

Earthquake events can cause affected households to relocate. Post-earthquake relocation disrupts displaced households’ social ties as well as their access to affordable services. Simulation models that capture post-earthquake relocation decision-making can be useful tools for supporting the development of related disaster risk reduction policies that aim at mitigating disaster-induced relocation. Yet, existing versions of these models focus particularly on housingrelated factors (e.g., housing repair costs), which are not the sole driver of post-earthquake relocation. In this paper, we integrate data-driven approaches and local perspectives into an existing simulation-based framework to holistically capture various context-specific factors perceived as being important to household relocation decision-making. The enhanced framework is used to quantitatively assess the effectiveness of various disaster risk reduction policies - both ‘soft’ (e.g., post-earthquake livelihood assistance funds) and ‘hard’ (e.g., upgrading existing infrastructure facilities to higher building codes) - in reducing post-earthquake household relocation, with an explicit focus on low-income households. We demonstrate it using a possible future (50-year) projection of “Tomorrowville”, a synthetic expanding urban extent that imitates a Global South setting. Our analyses suggest that livelihood assistance funds are more successful and pro-poor when it comes to mitigating positive post-earthquake relocation decision-making than hard policies focused on strengthening buildings (at least in the context of the examined case study)