Mitochondrial DNA metabolism is coupled with 20S proteasome function via regulation of deoxyribonucleotide homeostasis in Saccharomyces cerevisiae

The synthesis of mitochondrial DNA (mtDNA) is not coupled with cell cycle. Previous studies have shown that the size of deoxyribonucleoside triphosphate (dNTP) pools plays an important role in regulating mtDNA replication and amplification. In yeast, dNTPs are synthesized by the cytosolic ribonucleotide reductase (RNR). It is currently poorly understood as to how RNR activity is regulated in non-dividing or quiescent cells to finely tune mtDNA metabolism to cope with different metabolic states. Here, we show that defect in the 20S proteasome drastically destabilizes mtDNA. The mtDNA instability phenotype in 20S proteasome mutants is suppressed by overexpression of RNR3 or by the deletion of SML1, encoding a minor catalytic subunit and an intrinsic inhibitor of RNR respectively. We found that Sml1 is stabilized in the 20S proteasomal mutants, suggesting that 20S affects mtDNA stability by stabilizing Sml1. Interestingly, defect in the regulatory 19S proteasomal function has only subtle effect on mtDNA stability, supporting a role of the 20S proteasome in dNTP homeostasis independent of 19S. Finally, we found that when cells are transitioned from glycolytic to oxidative growth, Sml1 level is reduced in a 20S-dependent manner. In summary, our study establishes a link between cellular proteostasis and mtDNA metabolism through the regulation of dNTP homeostasis. We propose that increased degradation of Sml1 by the 20S proteasome under respiratory conditions provides a mechanism to stimulate dNTP synthesis and promote mtDNA amplification.

Predicting the Number of GHB-Related Toxicologic Admissions Using Google Trends Data

In the era of novel psychoactive substances (NPS), the internet became a relevant source of information and purchase for those who consume psychoactive drugs. Parallelly, a growing body of research aim to utilize web search metrics (most commonly by relying on Google Trends data) in the prediction of substance use-related trends, including epidemiological forecasting. The main goal of the current study was to assess the utility of web search queries in the prediction of Gamma-hydroxybutyrate (GHB)-related toxicologic admissions in Hungary by performing additive decomposition of time series to identify trend and seasonal components. Monthly data identified GHB-related search volume representing nationwide web interest towards this substance was found to be a significant covariate of admission rates; the seasonal component showed two peaks in the admission rates: one in December/January and another one in May, whereas more admissions on the weekends were observed as compared to weekday data in Hungary. By taking into account the subtle effect sizes of this study, these results suggest that Google Trends data may be useful in forecasting toxicologic admissions on a monthly level, yet a number of limitations should be considered when interpreting these associations. Web search metrics can therefore be used for early warning purposes in the field of toxicology as well. An external validation approach is also suggested by the authors.

Thermal Stability of Gel Foams Stabilized by Xanthan Gum, Silica Nanoparticles and Surfactants

The foams stabilized by nanoparticles (NPs), water-soluble polymers, and surfactants have potential application prospects in the development of new, environmentally friendly firefighting foams. In the present study, a gel foam containing a water-soluble polymer (xanthan gum, XG), hydrophilic silica NPs, hydrocarbon surfactant (SDS), and fluorocarbon surfactant (FS-50) were prepared. The surface activity, conductivity, viscosity, and foaming ability of foam dispersions were characterized. The gel foam stability under a radiation heat source and temperature distribution in the vertical foam layer were evaluated systematically. The results show that the addition of NPs and XG has a significant effect on the foaming ability, viscosity and foam thermal stability, but has a very subtle effect on the conductivity and surface activity. The foaming ability of the FS-50/SDS solution was enhanced by the addition of NPs, but decreased with increasing the XG concentration. The thermal stability of the foams stabilized by SDS/FS-50/NPs/XG increased with the addition of NPs and increasing XG concentration. Foam drainage and coarsening were significantly decelerated by the addition of NPs and XG. The slower foam drainage and coarsening are the main reason for the intensified foam thermal stability. The results obtained from this study can provide guidance for developing new firefighting foams.

Ionic and Enzymatic Multiple-Crosslinked Nanogels for Drug Delivery

Both ionic and enzymatic crosslink are efficient strategies for constructing network materials of high biocompatibility. Here chitosan was modified firstly and then crosslinked by these two methods for complementary advantages. The preparation methods and ionic crosslinkers can regulate the size and uniformity of the multiple-crosslinked nanogels. The multiple-crosslinked nanogels with the smallest size and the best uniformity was selected for the drug delivery. The drug-loading content and encapsulation efficiency were up to 35.01 and 66.82%, respectively. Their release behaviours are correlated with the pH value and the drug dosage. In general, the lower pH value and the lower drug dosage promoted the drug release. With the assistance of several kinetic models, it is found that drug diffusion plays a preponderant role in drug release, while polymer relaxation has a subtle effect. The multiple-crosslink resulting from ionic compounds and enzymes may provide a new perspective on developing novel biocompatible materials.

Substrate specificity of CYP2D6 genetic variants

Genetic variation in the gene encoding CYP2D6 is used to guide drug prescribing in clinical practice. However, genetic variants in CYP2D6 show substrate-specific effects that are currently not accounted for. With a systematic literature, we retrieved 22 original studies describing in vitro experiments focusing on CYP2D6 alleles ( CYP2D6*1, *2, *10 and *17) and substrates. Allele activity (clearance of the allele of interest divided by the clearance of the wildtype) was extracted. The results support the hypothesis of the existence of substrate specificity of the CYP2D6*17-allele (higher debrisoquine clearance), a subtle effect of the CYP2D6*10-allele (lower dextromethorphan clearance) but no substrate-specific effect of the CYP2D6*2-allele. Although our results support substrate specificity, for most substrates data are too sparse and require further studies.

Research on Explicit and Implicit Activities in Middle School Moral Education

Middle school moral education not only plays the role of guidance, motivation, and assurance in adolescent education and school work but also has great significance in promoting social civilization and progress. In order to make moral education become more permeable, vivid, and colorful, it is required to persuade people with reason and move a man with emotion, so as to achieve a subtle effect. Also, it builds an explicit and implicit system by exploring the middle school moral education practices. The explicit moral education activities and implicit moral education activities are inextricably linked as a joint force, which makes the school moral education work quite effective. In the former one, it makes further practical and exploration activities in developing the class moral education, upholding the theme and etiquette education of “the Four Cardinal Principles”, inheriting the "benevolence" value of education and practice education, and resisting the bad information about the moral education. The latter one, it focuses on the following three aspects of implicit moral education: teachers' virtue and deeds, family education, and game activities.

A Study on the Hair Improvement Effect of Dongbaek Oil on Dye Hair

This study used camellia oil, a natural ingredient, to study whether camellia oil has the effect of improving the hair quality damaged by dyeing. first, In order to find out the change in chromaticity of dyed hair due to the content of camellia oil, L*, a*, and b* value measurement were performed. As a result, Through the L* value of the dyed hair according to the camellia oil content, it was found that the dyed hair containing 2 g of camellia oil had a subtle effect of color clarity and dyeability. There was also less fading. In order to determine the degree of damage to the hair, the absorbance measurement using methylene blue showed a decrease in the average in hairs dyed with 2 g of camellia oil, indicating that there was a hair improvement effect in hairs dyed with camellia oil. As a result of studying whether the hair dye containing camellia oil has the effect of improving hair quality, the absorption strength decreased and the tensile strength increased. In addition, absorbance measurement, gloss measurement, and SEM (Scanning Electron Microscope) experiments were conducted. As a result, It was confirmed that there is an effect of improving hair quality in terms of the constant arrangement of cuticles on the hair surface and increasing the gloss of the hair. It was found that camellia oil, a natural ingredient, has a high effect on improving hair quality of dyed hair in order to minimize damage to dyed hair.

Mitochondria decode firing frequency and coincidences of postsynaptic APs and EPSPs

Mitochondrial metabolism is critical for brain function. However, the mechanisms linking mitochondrial energy production to neuronal activity are elusive. Using whole-cell electrical recordings from Layer 5 pyramidal neurons in cortical slices and fluorescence imaging of cytosolic, mitochondrial Ca2+ indicators and endogenous NAD(P)H, we revealed ultra-fast, spike-evoked mitochondrial Ca2+ transients temporally similar to cytosolic Ca2+ elevations. We demonstrate that, whereas single or few spikes elicit the mitochondrial Ca2+ transients throughout the cell, their amplitude is differentially regulated in distinct neuronal compartments. Thus, these signals were prominent in the soma and apical dendrites and ~3 times smaller in basal dendrites and axons. The spike firing frequency had a subtle effect on the amplitude of the cytosolic Ca2+ elevations but dramatically affected mitochondrial Ca2+ transients and NAD(P)H oxidation and recovery rates. Moreover, while subthreshold EPSPs alone caused no detectable Ca2+ elevation in dendritic mitochondria, the Hebbian coincidence of unitary EPSP and postsynaptic spike produced a localized, single mitochondrial Ca2+ elevation. These findings suggest that neuronal mitochondria are uniquely capable of decoding firing frequency and EPSP-to-spike time intervals for tuning the metabolic rate and triggering changes in synaptic efficacy.

Elastocaloric-effect-induced adiabatic magnetization in paramagnetic salts due to the mutual interactions

The temperature change under adiabatic stress, i.e., the elastocaloric effect, is a well-understood phenomenon and of particular interest due to its potential application in alternative ways for refrigeration. Here, we demonstrate that in the regime of low-temperatures (a few mK) real paramagnets can be magnetized when compressed adiabatically without applied magnetic field. Such adiabatic magnetization is a genuine many-body problem, stemming from the inherent dipolar mutual interactions between adjacent magnetic moments. We showcase experimental setups to carry out adiabatic magnetization and thus to access such a subtle effect. Perspectives of further investigations by controlling the mutual interactions in Bose–Einstein condensates in magnetic insulators and dipolar spin-ice systems via the adiabatic increase of temperature are also presented. Yet, we discuss the connection between the elastic Grüneisen parameter and the shift on the critical temperature of second-order phase transitions under adiabatic stress, as well as its connection with the Ehrenfest relation.