Impact of protein and small molecule interactions on kinase conformations.

Protein kinases act as central molecular switches in the control of cellular functions. Alterations in the regulation and function of protein kinases may provoke diseases including cancer. In this study we investigate the conformational states of such disease-associated kinases using the high sensitivity of the kinase conformation (KinCon) reporter system. We first track BRAF kinase activity conformational changes upon melanoma drug binding. Second, we also use the KinCon reporter technology to examine the impact of regulatory protein interactions on LKB1 kinase tumor suppressor functions. Third, we explore the conformational dynamics of RIP kinases in response to TNF pathway activation and small molecule interactions. Finally, we show that CDK4/6 interactions with regulatory proteins alter conformations which remain unaffected in the presence of clinically applied inhibitors. Apart from its predictive value, the KinCon technology helps to identify cellular factors that impact drug efficacies. The understanding of the structural dynamics of full-length protein kinases when interacting with small molecule inhibitors or regulatory proteins is crucial for designing more effective therapeutic strategies.

Correcting directional dark field x-ray imaging artefacts using position dependent image deblurring and attenuation removal.

In recent years, a novel x-ray imaging modality has emerged that reveals unresolved sample microstructure via a "dark-field image", which provides complementary information to conventional "bright-field" images, such as attenuation and phase-contrast modalities. This x-ray dark-field signal is produced by unresolved microstructures scattering the x-ray beam resulting in localised image blur. Dark-field retrieval techniques extract this blur to reconstruct a dark-field image. Unfortunately, the presence of non-dark-field blur such as source-size blur or the detector point-spread-function can affect the dark-field retrieval as they also blur the experimental image. In addition, dark-field images can be degraded by the artefacts induced by large intensity gradients from attenuation and propagation-based phase contrast, particularly around sample edges. By measuring any non-dark-field blurring across the image plane and removing it from experimental images, as well as removing attenuation and propagation-based phase contrast, we show that a directional dark-field image can be retrieved with fewer artefacts and more consistent quantitative measures. We present the details of these corrections and provide "before and after" directional dark-field images of samples imaged at a synchrotron source. This paper utilises single-grid directional dark-field imaging, but these corrections have the potential to be broadly applied to other x-ray imaging techniques.

Sensing mechanism of the benzo-bodipy based fluorescent probe for Hypochlorous acid detection: Invalidity of photoinduced electron transfer.

In vivo real-time detection of hypochlorous acid (HClO) in biological systems plays a crucial role in diagnosing immune-related diseases. Experimentally, a benzo-bodipy probe based on the photo-induced electron transfer (PeT) sensing mechanism has been developed for live fluorescence imaging. However, there have been no theoretical studies conducted to substantiate the precision of the sensing mechanism. This paper employs density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods to investigate the fluorescence detection mechanism of benzo-bodipy derivatives (BBy-T and BBy-TO), proposing a detection approach based on dark nπ* state quenching. The study reveals that the fluorescence quenching mechanism of BBy-T is primarily regulated by a thiomorpholine moiety, involving a dark nπ* state transition non-radiatively. Furthermore, this paper explains the fluorescence enhancement observed in BBy-TO. Theoretical investigations demonstrate, based on frontier molecular orbitals (FMOs) and hole-electron analysis, that the fluorescence enhancement for BBy-TO is not governed by the previously proposed intramolecular charge transfer (ICT) mechanism in experiments but rather follows a locally excited (LE) ππ* pattern. This work offers new insights for the design of novel fluorescence probes based on bodipy and benzo derivatives, expanding the understanding of their fluorescence properties.

Sequential window acquisition of all theoretical mass spectra (SWATH-MS) as an emerging proteomics approach for the discovery of dark-cutting beef biomarkers.

Recent advances in "omics" technologies have enabled the identification of new beef quality biomarkers and have also allowed for the early detection of quality defects such as dark-cutting beef, also known as DFD (dark, firm, and dry) beef. However, most of the studies conducted were carried out on a small number of animals and mostly applied gel-based proteomics. The present study proposes for the first time a Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) proteomics approach to characterize and comprehensively quantify the post-mortem muscle proteome of DFD (pH24 ≥ 6.2) and CONTROL (5.4 ≤ pH24 ≤ 5.6) beef samples within the largest database of DFD/CONTROL beef samples to date (26 pairs of the Longissimus thoracis muscle samples of young bulls from Asturiana de los Valles breed, n = 52). The pairwise comparison yielded 35 proteins that significantly differed in their abundances between the DFD and CONTROL samples. Chemometrics methods using both PLS-DA and OPLS-DA revealed 31 and 36 proteins with VIP > 2.0, respectively. The combination of different statistical methods these being Volcano plot, PLS-DA and OPLS-DA allowed us to propose 16 proteins as good candidate biomarkers of DFD beef. These proteins are associated with interconnected biochemical pathways related to energy metabolism (DHRS7B and CYB5R3), binding and signaling (RABGGTA, MIA3, BPIFA2B, CAP2, APOBEC2, UBE2V1, KIR2DL1), muscle contraction, structure and associated proteins (DMD, PFN2), proteolysis, hydrolases, and activity regulation (AGT, C4A, GLB1, CAND2), and calcium homeostasis (ANXA6). These results evidenced the potential of SWATH-MS and chemometrics to accurately identify novel biomarkers for meat quality defects, providing a deeper understanding of the molecular mechanisms underlying dark-cutting beef condition.

Dark Morph of the Oriental Honey-Buzzard (Pernis ptilorhynchus orientalis) is Attributable to Specific MC1R Haplotypes.

A thorough understanding of the development of complex plumages in birds necessitates the acquisition of genetic data pertaining to the mechanism underlying this phenomenon from various avian species. The oriental honey-buzzard (Pernis ptilorhynchus orientalis), a tropical summer migrant to Northeast Asia, including Japan, exemplifies this aspect owing to the diversity of its ventral coloration and intra-feather barring patterns. However, genetic polymorphism responsible for this diversity has not been identified yet. This study aimed to investigate the link between dark-plumed phenotypes of this subspecies and haplotypes of the melanocortin-1-receptor (MC1R) gene. A draft sequence of MC1R was constructed using next generation sequencing and subsequently amplified using designed polymerase chain reaction (PCR) primers. The genome sequences of 32 honey-buzzard individuals were determined using PCR, and 12 MC1R haplotype sequences were obtained. Among these haplotypes, we found that unique haplotypes with nine non-synonymous substitutions and four or five synonymous substitutions in the coding region had a perfect correlation with the dark-plumed phenotype. The lack of correlation between the genotype of ASIP coding region and plumage phenotype reiterated that the dark morph is attributable to specific MC1R haplotypes. The absence of a correlation between genetic polymorphisms of MC1R and the intra-feather barring patterns, as well as the diversity observed within lighter ground color classes (pale and intermediate), implies the involvement of alternative molecular mechanisms in the manifestation of the aforementioned phenotypes.

Oral Manifestations of Parry-Romberg Syndrome: A Case Report.

Parry-Romberg syndrome is a rare acquired disorder characterized by unilateral idiopathic progressive atrophy of the skin and soft tissues of the face, resulting in a sunken appearance. The muscles, cartilage, and underlying bony structures may also be affected. The etiology remains unclear and is based on several hypotheses. The incoherence of atrophy and the development of associated symptoms make the diagnosis, prognosis, and management of patients difficult. Here, we report the case of a 10-year-old boy who presented to the Department of Pediatric Dentistry at the Mohamed V Military Training Hospital in Rabat with progressive left hemifacial atrophy and was diagnosed by a pediatric rheumatologist as having Parry-Romberg syndrome. On extraoral examination, the patient presented a slight facial asymmetry and a small, dark, linear scar in the left zygomatic region. Intraoral examination revealed a left lateral open bite and atrophy of the left side of the tongue. Panoramic radiography showed incomplete eruption of the left mandibular first and second premolars (34/35), with significant root atrophy giving a narrowed appearance to the corresponding pulp chambers confirmed on retro alveolar radiographs. The mandible had a slightly reduced ramus height on the affected side confirming the patient's facial asymmetry. A better understanding of this syndrome will help to improve oral care in young patients.

Bioconversion of industrial wastes to hydrogen: A review on waste-to-wealth technologies.

Energy plays a significant role in attaining the sustainable growth of the industrial sector of any nation. The resources for getting energy are limited and cannot fulfill the huge demand for energy supply in the near future. Generating fuels from various waste materials and biomass is widely viewed as a sustainable energy source and a viable option for the future. Currently, researchers are particularly interested in synthesizing hydrogen (H2) without emitting CO2 and other greenhouse gases (GHGs). Hydrogen is recognized as a pristine and environmentally friendly energy source, presenting an optimal substitute for fossil fuels due to its high energy content of 122 kJg-1. The traditional methods for the production of H2 are cost-intensive and heavy input requirements are needed. Thus, the synthesis of H2 through biological approaches is cost-effective and eco-friendly alternating with easy operational requirements with ambient reaction conditions. The most common drawback of the biological production of H2 is the low yield and production rates of gas during scale-up conditions. This review is focused on different processes used to convert the wastes into H2 energy along with their pattern of utilization and the effect on the environment.

Investigating the physicochemical properties, sensory profile and consumer acceptability of beetroot dark chocolate.

BACKGROUND: The incorporation of functional food ingredients in chocolate that seek to eliminate, if not completely, most of the added sugar content, as well as the use of alternative chocolate production techniques, have gained popularity in recent years. This study aimed to incorporate red beetroot powder into dark chocolate and investigate the effect of red beetroot powder concentration and processing time in a melanger on the physicochemical properties, sensory profile and consumer acceptability of beetroot dark chocolate. RESULTS: The addition of red beetroot powder increased the moisture content, particle size distribution and hardness of the chocolates, while the opposite was true for processing time with no effect on the colour. Except for taste, which had an average score of 3.2 ± 1.8 on the 7-point hedonic scale, consumers scored all the other sensory attributes of the chocolates above 4.0. Among the chocolates with red beetroot powder, samples with a 15% red beetroot powder addition had a high average overall acceptability score of >5, while the 30% sample scored <4. CONCLUSION: Red beetroot powder can be used to replace sugar in dark chocolate without affecting its physicochemical properties, sensory profile or consumer acceptability. However, the target market should be considered when determining the level of red beetroot powder incorporation in terms of chocolate taste. This research has the potential to improve the overall health-promoting properties of dark chocolate by eliminating added sugar (partially or completely). It would also help to diversify beetroot utilization, allow small-scale processors to venture into chocolate production and expand the small-scale chocolate value chain. © 2024 Society of Chemical Industry.

Dark and light university: The relationship between dark and light personality traits and educational choices and the desire for power as a mediating factor.

The present research investigates the role of dark and light personality traits in determining academic discipline preferences among university students. Two studies showed that university students with relatively high scores on dark personality traits (specifically, narcissism and Machiavellianism) and relatively low scores on light personality traits are over-represented in business and law programs, compared to psychology and other academic disciplines. The results further suggest that personality is a distal determinant of academic discipline choice, with human values being the proximal determinant. Specifically, high scores in dark/low light personalities express a desire for power, which explains why they choose economics or law as their academic discipline. Contrary to our expectations, low dark/high light personalities were not over-represented in psychology, compared to other academic disciplines. Overall, our findings highlight the importance of considering personality traits and human values in understanding academic discipline choices among university students. Recognizing these factors can inform educational institutions in developing strategies to better support students in aligning their academic pursuits with their personal characteristics and values.

Photochargeable Mn-Based Metal-Organic Framework and Decoupled Photocatalysis.

Designing multifunctional materials that mimic the light-dark decoupling of natural photosynthesis is a key challenge in the field of energy conversion. Herein, we introduce MnBr-253, a precious metal-free metal-organic framework (MOF) built on Al nodes, bipyridine linkers and MnBr(CO)3(bipyridine) complexes. Upon irradiation, MnBr-253 colloids demonstrate an electron photocharging capacity of ~42 C ⋅ g-1 MOF, with state-of-the-art photocharging rate (1.28 C ⋅ s-1 ⋅ g-1 MOF) and incident photon-to-electron conversion efficiency of ~9.4 % at 450 nm. Spectroscopic and computational studies support effective electron accumulation at the Mn complex while high porosity and Mn loading account for the notable electron storage performance. The charged MnBr-253 powders were successfully applied for hydrogen evolution under dark conditions thus emulating the light-decoupled reactivity of photosynthesis.

Deciphering the dual role of persistent luminescence materials: Toxicity and photoreception effects on rice development.

Studies on the toxicity of micro- and nanomaterials in plants have primarily focused on their intrinsic effects. However, there is often oversight when considering the potential perceptual responses that plants may exhibit in response to these materials. In this investigation, we assessed the impact of three commercially available persistent luminescence materials (PLMs) that emit red, green, or blue light under various environmental conditions. We subjected rice (Oryza sativa L.), a short-day plant, to nine distinct treatments, including exposure to particles in isolation, their nocturnal afterglow, or a combination of both. We thoroughly examined rice seedling morphology, photosynthesis patterns, metabolite dynamics, and flowering gene expression to determine the biological responses of plants to these particles. These findings demonstrated that PLMs stably interact with rice, and their emitted afterglow precisely matches the perceptual bandwidth of rice photoreceptors. Notably, the nocturnal afterglow from the red and blue PLMs enhanced the vegetative growth of rice seedlings while inhibiting their reproductive development. The blue PLMs exhibited the most pronounced positive effects, while the red PLMs exhibited inhibitory effects. When exposed to a combination of red and blue PLMs, rice displays enhanced growth and development. The observed alterations in the expression patterns of genes responsible for flowering supported these effects. We concluded that PLMs influence rice growth and development due to their inherent properties and intermittent illumination during dark periods. Both factors collectively shape rice growth and development.

Isolation and molecular characterization of a novel relapsing fever group Borrelia from the white-eared opossum Didelphis albiventris in Brazil.

This study aimed to detect, isolate and to characterize by molecular methods a relapsing fever group (RFG) Borrelia in white-eared opossums (Didelphis albiventris) from Brazil. During 2015-2018, when opossums (Didelphis spp.) were captured in six municipalities of the state of São Paulo, Brazil, molecular analyses revealed the presence of a novel RFG Borrelia sp. in the blood of seven opossums (Didelphis albiventris), out of 142 sampled opossums (4.9% infection rate). All seven infected opossums were from a single location (Ribeirão Preto municipality). In a subsequent field study in Ribeirão Preto during 2021, two new opossums (D. albiventris) were captured, of which one contained borrelial DNA in its blood. Macerated tissues from this infected opossum were inoculated into laboratory animals (rodents and rabbits) and two big-eared opossums (Didelphis aurita), which had blood samples examined daily via dark-field microscopy. No spirochetes were visualized in the blood of the laboratory animals. Contrastingly, spirochetes were visualized in the blood of the two D. aurita opossums between 12 and 25 days after inoculation. Blood samples from these opossums were used for a multi-locus sequencing typing (MLST) based on six borrelial loci. Phylogenies inferred from MLST genes positioned the sequenced Borrelia genotype into the RFG borreliae clade basally to borreliae of the Asian-African group, forming a monophyletic group with another Brazilian isolate, "Candidatus B. caatinga". Based on this concatenated phylogenetic analysis, which supports that the new borrelial isolate corresponds to a putative new species, we propose the name "Candidatus Borrelia mimona".

Identification of Semiconductor Nanocrystals with Bright Ground-State Excitons.

While semiconductor nanocrystals provide versatile fluorescent materials for light-emitting devices, their brightness suffers from the "dark exciton"─an optically inactive electronic state into which nanocrystals relax before emitting. Recently, a theoretical mechanism, the Rashba effect, was discovered that can overcome this limitation by inverting the lowest-lying levels and creating a bright excitonic ground state. However, no methodology is available to systematically identify materials that exhibit this inversion, hindering the development of superbright nanocrystals and their devices. Here, based on a detailed understanding of the Rashba mechanism, we demonstrate a procedure that reveals previously unknown "bright-exciton" nanocrystals. We first define physical criteria to reduce over 500,000 known solids to 173 targets. Higher-level first-principles calculations then refine this list to 28 candidates. From these, we select five with high oscillator strength and develop effective-mass models to determine the nature of their lowest excitonic state. We confirm that four of the five solids yield bright ground-state excitons in nanocrystals. Thus, our results provide a badly needed roadmap for experimental investigation of bright-exciton nanomaterials.

Four years of climate warming reduced dark carbon fixation in coastal wetlands.

Dark carbon fixation (DCF), conducted mainly by chemoautotrophs, contributes greatly to primary production and the global carbon budget. Understanding the response of DCF process to climate warming in coastal wetlands is of great significance for model optimization and climate change prediction. Here, based on a four-year field warming experiment (average annual temperature increase of 1.5°C), DCF rates were observed to be significantly inhibited by warming in coastal wetlands (average annual DCF decline of 21.6%, and estimated annual loss of 0.08-1.5 Tg C yr-1 in global coastal marshes), thus causing a positive climate feedback. Under climate warming, chemoautotrophic microbial abundance and biodiversity, which were jointly affected by environmental changes such as soil organic carbon and water content, were recognized as significant drivers directly affecting DCF rates. Metagenomic analysis further revealed that climate warming may alter the pattern of DCF carbon sequestration pathways in coastal wetlands, increasing the relative importance of the 3HP/4HB cycle, whereas the relative importance of the dominant chemoautotrophic carbon fixation pathways (CBB cycle and W-L pathway) may decrease due to warming stress. Collectively, our work uncovers the feedback mechanism of microbially mediated DCF to climate warming in coastal wetlands, and emphasizes a decrease in carbon sequestration through DCF activities in this globally important ecosystem under a warming climate.

Unveiling the evolution of rotating black holes in loop quantum cosmology.

In this work, we aim to discuss about the evolution of rotating black holes (RBHs) within the context of loop quantum cosmology. Here, the main part of our research work focuses on the impacts of angular momentum based rotating parameter and accretion efficiency on the lifetime of RBHs. Our study reveals that accretion of dark energy would not significantly affect the evolution of RBHs, however higher value of rotating parameter could slightly delay the evaporation times of RBHs. Our analysis also depicts that the maximum value of rotating parameter for evolution of any RBH is 10 - 8 M i 2 , where M i is the formation mass of RBH. Moreover, from our calculation we found that the maximum mass of a presently existing supermassive black hole would be 10 48 g , if it undergoes rotation. Also from astrophysical constraint analysis, we found that there is a greater tendency for formation of black holes in loop quantum cosmology than standard model of cosmology.

Shining the "Light" on Moral Foundations: Light Versus Dark Personality Relates More Strongly to Moral Foundations.

Endorsement of the moral foundations specified by Moral Foundations Theory (MFT) can sometimes fail to relate negatively to certain dispositions indicative of bad moral character. This evidence has fueled some concerns over whether the moral foundations in MFT are "moral." To increase understanding of how moral foundations relate to moral character, we proposed the "asymmetry hypothesis." This hypothesis states that "good" character is a more powerful predictor of each moral foundation than "bad" character. Put differently, there is an asymmetry in the strength (not merely direction) with which the moral foundations relate to encompassing indicators of good versus bad character. This is important because it suggests that links between the moral foundations and moral character will be somewhat concealed by focusing on bad character and/or not considering encompassing indicators of good character. A sample of college participants (N = 514) rated their endorsement of moral foundations and completed two sets of measures that represented encompassing indicators of both good and bad character. The data supported the asymmetry hypothesis: Each encompassing good-character assessment was a stronger predictor of each moral foundation than its corresponding encompassing bad-character assessment. Furthermore, variance unique to any good-character assessment had about moderate relations with each moral foundation, but variance unique to any bad-character assessment had no more than small relations with each moral foundation. The study provides a more nuanced understanding of how moral character relates to moral foundations and highlights utility in considering moral character as multidimensional.

The impact of estrous cycle on anxiety-like behaviour during unlearned fear tests in female rats and mice: A systematic review and meta-analysis.

Anxiety fluctuates across the human menstrual cycle, with symptoms worsening during phases of declining or low ovarian hormones. Similar findings have been observed across the rodent estrous cycle, however, the magnitude and robustness of these effects have not been meta-analytically quantified. We conducted a systematic review and meta-analysis of estrous cycle effects on anxiety-like behaviour (124 articles; k = 259 effect sizes). In both rats and mice, anxiety-like behaviour was higher during metestrus/diestrus (lower ovarian hormones) than proestrus (higher ovarian hormones) (g = 0.44 in rats, g = 0.43 in mice). There was large heterogeneity in the data, which was partially accounted for by strain, experimental task, and reproductive status. Nonetheless, the effect of estrous cycle on anxiety-like behaviour was highly robust, with the fail-safe N test revealing the effect would remain significant even if 21,388 additional studies yielded null results. These results suggest that estrous cycle should be accounted for in studies of anxiety in females. Doing so will facilitate knowledge about menstrual-cycle regulation of anxiety disorders in humans.

Influences of bisphenol A on hydrogen production from food waste by thermophilic dark fermentation.

The extensive use of plastic products in food packaging and daily life makes them inevitably enter the treatment process of food waste (FW). Plasticizer as a new pollutant is threatening the dark fermentation of FW. Our study showed that bisphenol A (BPA) at > 250 mg/L had a significant inhibition on hydrogen production from FW by thermophilic dark fermentation. The endogenous ATP content and lactate dehydrogenase (LDH) release showed that high level of BPA not only inhibited the growth of hydrogen-producing consortium, but also led to cell death. In addition, BPA mainly affects the hydrogen-producing consortium by reducing cell membrane fluidity, damaging cell membrane integrity and reducing cell membrane potential, resulting in cell death. This study provides some new insights into the mechanism of the effect of BPA on hydrogen production from FW by thermophilic dark fermentation, and lays the foundation on the utilization of FW.

The mediating effects of moral disengagement and aggressive humor style: Dark Triad traits and schadenfreude.

Background: While schadenfreude is commonly experienced in interpersonal relationships, it is generally considered immoral. Although previous research has explored the factors relating to schadenfreude, including certain personality traits, moral disengagement, and humor styles, our understanding of these factors remains limited. The present study examined the mediating effects of moral disengagement and aggressive humor style in the relationship between the Dark Triad traits and schadenfreude. Methods: In this study, a sample of 693 Iranian students (69.4% female), was recruited using a convenient sampling method, consisting of 330 undergraduate, 230 graduate, and 133 Ph.D. students. The trait schadenfreude scale, the short Dark Triad, the moral disengagement scale, and the aggressive humor style scale were measured through an online survey. Results: The study found that Machiavellianism, narcissism, and psychopathy were positively related to schadenfreude, aggressive humor style, and moral disengagement. Additionally, aggressive humor style and moral disengagement mediated the relationship between Machiavellianism, narcissism, and psychopathy with schadenfreude. Conclusion: This study provides insights into the complex relationships between Dark Triad traits, moral disengagement, aggressive humor style, and schadenfreude. The findings suggest that individuals with higher levels of Dark Triad traits may be more likely to experience pleasure from others' misfortunes. Furthermore, the study highlights the importance of moral disengagement and aggressive humor style as potential mechanisms underlying the relationship between Dark Triad traits and schadenfreude. Further research should be done to explore the motivational factors influencing schadenfreude in specific settings, thereby elucidating these connections.

Estimates of the vitality and performances of Apis mellifera mellifera and hybrid honey bee colonies in Siberia: a 13-year study.

Honeybees display a great range of biological, behavioral, and economic traits, depending on their genetic origin and environmental factors. The high diversity of honeybees is the result of natural selection of specific phenotypes adapted to the local environment. Of particular interest is adaptation of local and non-local bee colonies to environmental conditions. To study the importance of genotype-environment interactions on the viability and productivity of local and non-local bee colonies, we analyzed the long-term dynamics of the main traits in dark forest bees (Apis mellifera mellifera) and hybrid colonies. From 2010 to 2022, a total of 64 colonies living in an apiary in Siberia, Russia, were monitored and tested to assess their biological, behavioral, and economic traits in a temperate continental climate. We detected significant correlations between the studied biological and behavioral indicators of the bee colony such as colony strength, overwintering ability, infection of colonies with diseases, hygienic behavior, and others. No relationships between the biological and economic (honey productivity) traits of bee colonies are shown. The overall result of our study is that local dark forest bee, A.m.mellifera, showed higher values for all analyzed traits than hybrid colonies. Compared to hybrids, dark forest bee colonies showed more gentleness, productivity, and survivorship. The results from our study indicate a specific local adaptation of the A.m.mellifera subspecies in a temperate continental climate. Siberia represents a unique region for the conservation of the dark forest bee. The creation of conservation areas is one way to protect local bee populations, well adapted to local environmental conditions, from uncontrolled importation of bee breeds from different regions.