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1.
Heliyon ; 10(15): e35164, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39165944

RESUMO

The present study addresses a significant omission in the literature by examining the role of non-traditional financial organizations in poverty reduction. Previous research has primarily focused on the direct impact of commercial banks on poverty, neglecting the contribution of other types of financial institutions. This research posited that Islamic banks are anticipated to assume a pivotal function in mitigating poverty; nonetheless, more studies on the topic need to be conducted. This research used the Partial Least Squares Regression technique to investigate the impact of Islamic banks on poverty alleviation in several developing nations from 2013 to 2019. The empirical data demonstrates a direct correlation between the overall assets of Islamic banks and some evident characteristics. The heightened acquisition of holdings by Islamic banks indicates a decrease in poverty. Furthermore, a statistically significant correlation exists between the legal framework and poverty alleviation. It is crucial to acknowledge that the research is limited by the intrinsic limits imposed by the accessible information on Islamic banks and the specific temporal limitations of the study. Future academic research should aim to increase the sample size and cultural and social factors and expand the time frame to understand the intricate function of Islamic banks in reducing poverty entirely. This paper is helpful to many policymakers in developing countries, including Hail development plans in Saudi Arabia.

2.
Plant Physiol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39106412

RESUMO

Ascorbate is a major plant metabolite that plays crucial roles in various processes, from reactive oxygen scavenging to epigenetic regulation. However, to what extent and how ascorbate modulates metabolism is largely unknown. We investigated the consequences of chloroplastic and total cellular ascorbate-deficiencies by studying chloroplastic ascorbate-transporter mutant lines lacking PHOSPHATE TRANSPORTER 4; 4 (PHT4; 4) , and the ascorbate-deficient vtc2-4 mutant of Arabidopsis (Arabidopsis thaliana). Under regular growth conditions, both ascorbate deficiencies caused minor alterations in photosynthesis, with no apparent signs of oxidative damage. In contrast, metabolomics analysis revealed global and largely overlapping alterations in the metabolome profiles of both ascorbate-deficiency mutants, suggesting that chloroplastic ascorbate modulates plant metabolism. We observed significant alterations in amino acid metabolism, particularly in arginine metabolism, activation of nucleotide salvage pathways, and changes in secondary metabolism. In addition, proteome-wide analysis of thermostability revealed that ascorbate may interact with enzymes involved in arginine metabolism, the Calvin-Benson cycle, and several photosynthetic electron transport components. Overall, our results suggest that, independently of oxidative stress, chloroplastic ascorbate modulates the activity of diverse metabolic pathways in vascular plants and may act as an internal metabolic signal.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39102142

RESUMO

This study investigates how carbon dioxide emissions, natural gas, energy consumption, energy investment, coal and crude oil, and per capita exports affected the economic growth of the United States from 1993 to 2023 using the Vector Error Correction (VEC) model. The findings highlight the importance of exports and energy investment in driving both short- and long-term economic growth, while also highlighting interactions between carbon emissions, coal use and crude oil. It was determined that changes in natural gas and exports affected energy investment in the short term, while coal and exports affected natural gas. These results provide valuable information about the dynamics of the American economy and contribute to our understanding of the complex interactions between various factors and their effects on economic growth, offering implications for further research and policy development to promote sustainable economic development.

4.
J Mol Biol ; 436(18): 168708, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009072

RESUMO

Nucleoside triphosphates are indispensable in numerous biological processes, with enzymes involved in their biogenesis playing pivotal roles in cell proliferation. Pyruvate kinase (PYK), commonly regarded as the terminal glycolytic enzyme that generates ATP in tandem with pyruvate, is also capable of synthesizing a wide range of nucleoside triphosphates from their diphosphate precursors. Despite their substrate promiscuity, some PYKs show preference towards specific nucleotides, suggesting an underlying mechanism for differentiating nucleotide bases. However, the thorough characterization of this mechanism has been hindered by the paucity of nucleotide-bound PYK structures. Here, we present crystal structures of Streptococcus pneumoniae PYK in complex with four different nucleotides. These structures facilitate direct comparison of the protein-nucleotide interactions and offer structural insights into its pronounced selectivity for GTP synthesis. Notably, this selectivity is dependent on a sequence motif in the nucleotide recognition site that is widely present among prokaryotic PYKs, particularly in Firmicutes species. We show that pneumococcal cell growth is significantly impaired when expressing a PYK variant with compromised GTP and UTP synthesis activity, underscoring the importance of PYK in maintaining nucleotide homeostasis. Our findings collectively advance our understanding of PYK biochemistry and prokaryotic metabolism.

5.
Front Public Health ; 12: 1411191, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081359

RESUMO

Objective: Although the regular exercise population is a key metric for gaging the success of China's fitness-for-all activities, effective policy approaches to increase mass sports participation remain unclear. Previous research suggests that GDP, educational attainment, sports resources, and meteorological conditions could influence regular exercise participation. Therefore, this study first analyzed the macro-level correlates influencing China's regular exercise population. Methods: We utilize ordinary least squares (OLS) regression and geographical weighted regression (GWR) to theorize the relationship. The analysis encompasses data from the 31 administrative regions of Mainland China, as reported at the end of the 13th Five-Year Plan period. The log-log model enables us to quantify the marginal effect (elasticity) of the explanatory variables. Results: The OLS regression showed that regional GDP and the proportion of the population with a university education were significant predictors. In the global model, the marginal effects of regional GDP and university education were 0.048 and 0.173, respectively. Furthermore, the GWR revealed a distinct geographic pattern that corresponds to the classic Hu Line. Conclusion: While regional GDP was also a significant correlate in our model, the elasticity demonstrates that university education had an asymmetric effect on China's regular exercise population. Therefore, this paper sheds light on a policy priority for the upcoming 15th Five-Year Plan, emphasizing the strategic importance of expanding university education to enhance mass sports participation. In turn, a better-educated populace may yield significant secondary effects on public health and contribute to the high-quality development of the Chinese path to modernization.


Assuntos
Desenvolvimento Econômico , Exercício Físico , Humanos , China , Universidades , Desenvolvimento Econômico/estatística & dados numéricos , Masculino , Escolaridade
6.
Afr J Reprod Health ; 28(5): 78-83, 2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38920270

RESUMO

This study utilized comprehensive graphical, descriptive and econometric methods to provide empirical answers to the nexus between government health expenditures and neonatal mortality in China. Secondary data from 2000 to 2021 was extracted from the World Development Indicators, after which it was analyzed empirically with the following results; in the past two decades, the incidence of neonatal death has reduced by 85%. Meanwhile, domestic general government health expenditure per capita ranged between $326.2 and $9.4 during the period with a mean value of $138. Average neonatal mortality rate recorded an approximately 10 deaths per 1000 live births, while government health expenditures and neonatal mortality showed a significant negative relationship in China. Therefore, this study confirms that China has been able to meet the SDG 3 with evidence indicating that this may be due to increased government health expenditure.


Cette étude a utilisé des méthodes graphiques, descriptives et économétriques complètes pour fournir des réponses empiriques au lien entre les dépenses publiques de santé et la mortalité néonatale en Chine. Les données secondaires de 2000 à 2021 ont été extraites des indicateurs de développement dans le monde, après quoi elles ont été analysées empiriquement avec les résultats suivants : au cours des deux dernières décennies, l'incidence des décès néonatals a diminué de 85 %. Dans le même temps, les dépenses de santé des administrations publiques nationales par habitant ont varié entre 326,2 et 9,4 dollars au cours de la période, avec une valeur moyenne de 138 dollars. Le taux de mortalité néonatale moyen a enregistré environ 10 décès pour 1 000 naissances vivantes, tandis que les dépenses publiques de santé et la mortalité néonatale ont montré une relation négative significative en Chine. Par conséquent, cette étude confirme que la Chine a été en mesure d'atteindre l'ODD 3 avec des preuves indiquant que cela pourrait être dû à l'augmentation des dépenses publiques de santé.


Assuntos
Gastos em Saúde , Mortalidade Infantil , Desenvolvimento Sustentável , Humanos , Gastos em Saúde/estatística & dados numéricos , China/epidemiologia , Mortalidade Infantil/tendências , Recém-Nascido , Lactente , Feminino , Governo
7.
Sensors (Basel) ; 24(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38894197

RESUMO

Spatialization and analysis of the gross domestic product of second and tertiary industries (GDP23) can effectively depict the socioeconomic status of regional development. However, existing studies mainly conduct GDP spatialization using nighttime light data; few studies specifically concentrated on the spatialization and analysis of GDP23 in a built-up area by combining multi-source remote sensing images. In this study, the NPP-VIIRS-like dataset and Sentinel-2 multi-spectral remote sensing images in six years were combined to precisely spatialize and analyze the variation patterns of the GDP23 in the built-up area of Zibo city, China. Sentinel-2 images and the random forest (RF) classification method based on PIE-Engine cloud platform were employed to extract built-up areas, in which the NPP-VIIRS-like dataset and comprehensive nighttime light index were used to indicate the nighttime light magnitudes to construct models to spatialize GDP23 and analyze their change patterns during the study period. The results found that (1) the RF classification method can accurately extract the built-up area with an overall accuracy higher than 0.90; the change patterns of built-up areas varied among districts and counties, with Yiyuan county being the only administrative region with an annual expansion rate of more than 1%. (2) The comprehensive nighttime light index is a viable indicator of GDP23 in the built-up area; the fitted model exhibited an R2 value of 0.82, and the overall relative errors of simulated GDP23 and statistical GDP23 were below 1%. (3) The year 2018 marked a significant turning point in the trajectory of GDP23 development in the study area; in 2018, Zhoucun district had the largest decrease in GDP23 at -52.36%. (4) GDP23 gradation results found that Zhangdian district exhibited the highest proportion of high GDP23 (>9%), while the proportions of low GDP23 regions in the remaining seven districts and counties all exceeded 60%. The innovation of this study is that the GDP23 in built-up areas were first precisely spatialized and analyzed using the NPP-VIIRS-like dataset and Sentinel-2 images. The findings of this study can serve as references for formulating improved city planning strategies and sustainable development policies.

8.
Healthcare (Basel) ; 12(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38891223

RESUMO

Life expectancy at birth is considered a parameter of the social development, health system, or economic development of a country. We aimed to investigate the effects of GDP per capita (as the economic factor), health care expenditure, the number of medical doctors (as social factors), and CO2 emissions (as the environmental factor) on life expectancy. We used panel data analysis for 13 Eastern European countries over the 2000-2020 period. After performing the analysis, we used a cross-country fixed-effects panel (GLS with SUR weights). According to our model, a one percent increase in health expenditure (as % of GDP) increases life expectancy at birth by 0.376 years, whereas each additional medical doctor per 10,000 inhabitants increases life expectancy at birth by 0.088 years on average. At the same time, each additional 10,000 USD per capita each year would increase life expectancy at birth by 1.8 years on average. If CO2 emissions increase by 1 metric ton per capita, life expectancy at birth would decrease by 0.24 years, suggesting that higher carbon emissions are capable of reducing longevity. Every European country has to make special efforts to increase the life expectancy of its inhabitants by applying economic and health policies focused on the well-being of the population.

9.
Int J Biochem Cell Biol ; 173: 106602, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38843991

RESUMO

Congenital disorders of glycosylation (CDG) are a large family of genetic diseases resulting from defects in the synthesis of glycans and the attachment of glycans to macromolecules. The CDG known as leukocyte adhesion deficiency II (LAD II) is an autosomal, recessive disorder caused by mutations in the SLC35C1 gene, encoding a transmembrane protein of the Golgi apparatus, involved in GDP-fucose transport from the cytosol to the Golgi lumen. In this study, a cell-based model was used as a tool to characterize the molecular background of a therapy based on a fucose-supplemented diet. Such therapies have been successfully introduced in some (but not all) known cases of LAD II. In this study, the effect of external fucose was analyzed in SLC35C1 KO cell lines, expressing 11 mutated SLC35C1 proteins, previously discovered in patients with an LAD II diagnosis. For many of them, the cis-Golgi subcellular localization was affected; however, some proteins were localized properly. Additionally, although mutated SLC35C1 caused different α-1-6 core fucosylation of N-glycans, which explains previously described, more or less severe disorder symptoms, the differences practically disappeared after external fucose supplementation, with fucosylation restored to the level observed in healthy cells. This indicates that additional fucose in the diet should improve the condition of all patients. Thus, for patients diagnosed with LAD II we advocate careful analysis of particular mutations using the SLC35C1-KO cell line-based model, to predict changes in localization and fucosylation rate. We also recommend searching for additional mutations in the human genome of LAD II patients, when fucose supplementation does not influence patients' state.


Assuntos
Fucose , Mutação , Humanos , Fucose/metabolismo , Síndrome da Aderência Leucocítica Deficitária/genética , Síndrome da Aderência Leucocítica Deficitária/metabolismo , Síndrome da Aderência Leucocítica Deficitária/patologia , Fenótipo , Glicosilação , Complexo de Golgi/metabolismo , Proteínas de Transporte de Nucleotídeos/genética , Proteínas de Transporte de Nucleotídeos/metabolismo , Polissacarídeos/metabolismo , Animais , Proteínas de Transporte de Monossacarídeos
10.
Prim Dent J ; 13(2): 26-28, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38888070

RESUMO

INTRODUCTION: With increasing numbers of oral cancer diagnoses and guidance recommending that patients approach their doctors or dentists for assessments, when searching for information regarding mouth cancer, patients may first look to their dental practice website. This study aimed to evaluate the variance of patient information provided regarding oral cancer on dental practice websites. MATERIALS AND METHODS: Dental practices within the Manchester area with an active website were included with assessment of whether there was any information provided regarding reducing oral cancer risk factors, signs to look out for and if oral cancer screening was included as part of the general check-up, using a three-point score based on the joint statement from the British and Irish Society for Oral Medicine (BISOM) and Cancer Research UK (CRUK) regarding oral cancer diagnosis and prevention. RESULTS: In total, 66.6% (n=60) of practices provided no accessible information regarding oral cancer screening and prevention on their websites. Only 12.2% (n=11) discussed all three factors of oral screening, symptoms and reducing risk factors. Screening as part of routine examination was most frequently mentioned at 27% (n=24), risk factors were discussed by 23% (n=21) of practices and symptoms to be aware of by 13% (n=12). DISCUSSION: There is a lack of information available to patients on dental practice websites regarding oral cancer. To overcome lack of quality assurance on the internet, dentists can provide factual information via their dental practice websites. This could help with improving patient awareness and therefore aiding in early detection, improving patient outcomes.


Assuntos
Internet , Neoplasias Bucais , Humanos , Neoplasias Bucais/diagnóstico , Fatores de Risco , Detecção Precoce de Câncer , Educação de Pacientes como Assunto , Informação de Saúde ao Consumidor/normas , Inglaterra
11.
J Exp Bot ; 75(9): 2599-2603, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38699987

RESUMO

This Special Issue was assembled to mark the 25th anniversary of the proposal of the d -mannose/ l -galactose (Smirnoff-Wheeler) ascorbate biosynthesis pathway in plants ( Wheeler et al., 1998 ). The issue aims to assess the current state of knowledge and to identify outstanding questions about ascorbate metabolism and functions in plants.


Assuntos
Ácido Ascórbico , Plantas , Ácido Ascórbico/metabolismo , Plantas/metabolismo
12.
J Mol Model ; 30(5): 157, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698260

RESUMO

CONTEXT: The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms. This study provides a significant contribution to understanding bilastine's polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products. METHODS: The molecular conformation of two bilastine forms was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311 + + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

13.
DNA Repair (Amst) ; 139: 103693, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776712

RESUMO

MutT proteins belong to the Nudix hydrolase superfamily that includes a diverse group of Mg2+ requiring enzymes. These proteins use a generalized substrate, nucleoside diphosphate linked to a chemical group X (NDP-X), to produce nucleoside monophosphate (NMP) and the moiety X linked with phosphate (XP). E. coli MutT (EcoMutT) and mycobacterial MutT1 (MsmMutT1) belong to the Nudix hydrolase superfamily that utilize 8-oxo-(d)GTP (referring to both 8-oxo-GTP or 8-oxo-dGTP). However, predominant products of their activities are different. While EcoMutT produces 8-oxo-(d)GMP, MsmMutT1 gives rise to 8-oxo-(d)GDP. Here, we show that the altered cleavage specificities of the two proteins are largely a consequence of the variation at the equivalent of Gly37 (G37) in EcoMutT to Lys (K65) in the MsmMutT1. Remarkably, mutations of G37K (EcoMutT) and K65G (MsmMutT1) switch their cleavage specificities to produce 8-oxo-(d)GDP, and 8-oxo-(d)GMP, respectively. Further, a time course analysis using 8-oxo-GTP suggests that MsmMutT1(K65G) hydrolyses 8-oxo-(d)GTP to 8-oxo-(d)GMP in a two-step reaction via 8-oxo-(d)GDP intermediate. Expectedly, unlike EcoMutT (G37K) and MsmMutT1, EcoMutT and MsmMutT1 (K65G) rescue an E. coli ΔmutT strain, better by decreasing A to C mutations.


Assuntos
Nucleotídeos de Desoxiguanina , Proteínas de Escherichia coli , Escherichia coli , Mycobacterium smegmatis , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Mycobacterium smegmatis/enzimologia , Mycobacterium smegmatis/metabolismo , Mycobacterium smegmatis/genética , Especificidade por Substrato , Nucleotídeos de Desoxiguanina/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/enzimologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Substituição de Aminoácidos , Pirofosfatases/metabolismo , Pirofosfatases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Guanosina Trifosfato/metabolismo , Guanosina Trifosfato/análogos & derivados
14.
Environ Sci Pollut Res Int ; 31(24): 35498-35518, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38724848

RESUMO

The rapid economic development leads to excessive consumption of fossil energy, resulting in a large number of carbon emissions, which makes the sustainable development of China's economy and society face great challenges. Under the background of global warming and environmental deterioration, developing low-carbon economy has become an inevitable choice for China to change its development model and improve its international competitiveness. Technological progress is the first driving force to promote economic growth. However, the influence degree and mechanism of technological progress on the development of low-carbon economy are still unclear. Based on this, the paper proposes the concept of low-carbon GDP, which is used to measure the low-carbon economic development of 30 Chinese provinces. Then, the panel fixed effect model is used to study the effect degree and mechanism of technological progress on low-carbon GDP and the moderating effect of other factors on the relationship between them. The results show that, first, economically developed provinces and regions have higher per capita low-carbon GDP and low-carbon GDP index, but the speed and quality of low-carbon economic development are not necessarily higher. Second, technological progress can promote the growth of low-carbon GDP and make greater contributions to resources-poor regions. Third, improving local education can make technological progress more effective in low-carbon economic development. China needs to upgrade technological development by developing new and high-tech technologies, promoting new urbanization and strengthening education in order to promote low-carbon economic development.


Assuntos
Carbono , Desenvolvimento Econômico , China , Aquecimento Global , Desenvolvimento Sustentável
15.
Microbiol Spectr ; 12(6): e0367323, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38722158

RESUMO

Xanthomonas citri subsp. citri (Xcc) is a bacterium that causes citrus canker, an economically important disease that results in premature fruit drop and reduced yield of fresh fruit. In this study, we demonstrated the involvement of XanB, an enzyme with phosphomannose isomerase (PMI) and guanosine diphosphate-mannose pyrophosphorylase (GMP) activities, in Xcc pathogenicity. Additionally, we found that XanB inhibitors protect the host against Xcc infection. Besides being deficient in motility, biofilm production, and ultraviolet resistance, the xanB deletion mutant was unable to cause disease, whereas xanB complementation restored wild-type phenotypes. XanB homology modeling allowed in silico virtual screening of inhibitors from databases, three of them being suitable in terms of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, which inhibited GMP (but not PMI) activity of the Xcc recombinant XanB protein in more than 50%. Inhibitors reduced citrus canker severity up to 95%, similarly to copper-based treatment. xanB is essential for Xcc pathogenicity, and XanB inhibitors can be used for the citrus canker control. IMPORTANCE: Xcc causes citrus canker, a threat to citrus production, which has been managed with copper, being required a more sustainable alternative for the disease control. XanB was previously found on the surface of Xcc, interacting with the host and displaying PMI and GMP activities. We demonstrated by xanB deletion and complementation that GMP activity plays a critical role in Xcc pathogenicity, particularly in biofilm formation. XanB homology modeling was performed, and in silico virtual screening led to carbohydrate-derived compounds able to inhibit XanB activity and reduce disease symptoms by 95%. XanB emerges as a promising target for drug design for control of citrus canker and other economically important diseases caused by Xanthomonas sp.


Assuntos
Proteínas de Bactérias , Citrus , Doenças das Plantas , Xanthomonas , Xanthomonas/enzimologia , Xanthomonas/genética , Xanthomonas/patogenicidade , Citrus/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Biofilmes/crescimento & desenvolvimento , Virulência
16.
Biophys Chem ; 309: 107234, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603989

RESUMO

Activation of heterotrimeric G-proteins (Gαßγ) downstream to receptor tyrosine kinases (RTKs) is a well-established crosstalk between the signaling pathways mediated by G-protein coupled receptors (GPCRs) and RTKs. While GPCR serves as a guanine exchange factor (GEF) in the canonical activation of Gα that facilitates the exchange of GDP for GTP, the mechanism through which RTK phosphorylations induce Gα activation remains unclear. Recent experimental studies revealed that the epidermal growth factor receptor (EGFR), a well-known RTK, phosphorylates the helical domain tyrosine residues Y154 and Y155 and accelerates the GDP release from the Gαi3, a subtype of Gα-protein. Using well-tempered metadynamics and extensive unbiased molecular dynamics simulations, we captured the GDP release event and identified the intermediates between bound and unbound states through Markov state models. In addition to weakened salt bridges at the domain interface, phosphorylations induced the unfolding of helix αF, which contributed to increased flexibility near the hinge region, facilitating a greater distance between domains in the phosphorylated Gαi3. Although the larger domain separation in the phosphorylated system provided an unobstructed path for the nucleotide, the accelerated release of GDP was attributed to increased fluctuations in several conserved regions like P-loop, switch 1, and switch 2. Overall, this study provides atomistic insights into the activation of G-proteins induced by RTK phosphorylations and identifies the specific structural motifs involved in the process. The knowledge gained from the study could establish a foundation for targeting non-canonical signaling pathways and developing therapeutic strategies against the ailments associated with dysregulated G-protein signaling.


Assuntos
Fatores de Troca do Nucleotídeo Guanina , Transdução de Sinais , Fosforilação , Fatores de Troca do Nucleotídeo Guanina/química , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Tirosina/metabolismo
17.
Methods Mol Biol ; 2797: 237-252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38570464

RESUMO

The activation level of RAS can be determined by GTP hydrolysis rate (khy) and GDP-GTP exchange rates (kex). Either impaired GTP hydrolysis or enhanced GDP-GTP exchange causes the aberrant activation of RAS in oncogenic mutants. Therefore, it is important to quantify the khy and kex for understanding the mechanisms of RAS oncogenesis and drug development. Conventional methods have individually measured the kex and khy of RAS. However, within the intracellular environment, GTP hydrolysis and GDP-GTP exchange reactions occur simultaneously under conditions where GTP concentration is kept constant. In addition, the intracellular activity of RAS is influenced by endogenous regulatory proteins, such as RAS GTPase activating proteins (GAPs) and the guanine-nucleotide exchange factors (GEFs). Here, we describe the in vitro and in-cell NMR methods to estimate the khy and kex simultaneously by measuring the time-dependent changes of the fraction of GTP-bound ratio under the condition of constant GTP concentration.


Assuntos
Fatores de Troca do Nucleotídeo Guanina , Proteínas Ativadoras de ras GTPase , Guanosina Trifosfato/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , Hidrólise , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Espectroscopia de Ressonância Magnética , Guanosina Difosfato/metabolismo
18.
Plant Physiol Biochem ; 210: 108649, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38653099

RESUMO

The translation elongation factor 1α (EF1α) protein is a highly conserved G protein that is crucial for protein translation in all eukaryotic organisms. EF1α quickly became insoluble at temperatures 42 °C treatment for 2h in vitro, but generally remained soluble in vivo even after being exposed to temperatures as high as 45 °C for an extended period, which suggests that protective mechanisms exist for keeping EF1α soluble in plant cells under heat stress. EF1α had fast in vivo insolubilization when exposed to 45 °C, resulting in about 40% of the protein aggregating after 9 h. Given its established role in protein translation, heat-induced aggregation is most likely to impact the function of the elongation factor. Overexpression of constitutive mutants in both GTP-bound and GDP-bound forms of EF1α resulted in significantly decreased heat tolerance. These findings provide evidence to support the critical role of EF1α, a thermosensitive protein, in the heat tolerance of plants.


Assuntos
Fator 1 de Elongação de Peptídeos , Termotolerância , Fator 1 de Elongação de Peptídeos/metabolismo , Fator 1 de Elongação de Peptídeos/genética , Termotolerância/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Temperatura Alta , Agregados Proteicos , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Resposta ao Choque Térmico/fisiologia
19.
J Fungi (Basel) ; 10(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38535216

RESUMO

GDP-mannose transporters (GMTs) have been implicated in the virulence of some important pathogenic fungi, and guanosine diphosphate (GDP) mannose transporters transport GDP-mannose from the cytosol to the Golgi lumen prior to mannosylation, where mannose attaches to the modified protein. GMTs could be potential targets for new antifungal drugs, as disruption of any step in GDP-mannose biosynthesis can affect fungal viability, growth, or virulence. To date, the GDP-mannose transporter has been extensively studied in yeast, but its biological function in fungi, particularly F. graminearum, is still unclear. In this experimental study, the role of the GDP-mannose transporter in F. graminearum was investigated by analysing the VRG4 gene. FgGmtA and FgGmtB were blastp-derived from their Scvrg4 protein sequences and proved to be their functional homologues. The mutant and complementary strains of FgGmtA, FgGmtB and FgGmtA&B genes were generated and used to evaluate the effect of the two GMTs genes on mycelial growth, asexual reproduction, sexual reproduction, cell wall sensitivity, glyphosate synthesis and drug susceptibility. Only in the FgGmtB and FgGmtA&B mutants was the rate of mycelial growth slowed, conidium production increased, sexual reproduction impaired, cell wall sensitivity increased, glycemic content decreased, and drug sensitivity reduced. The results of the pathogenicity assessment of GMTs showed that only FgGmtB affects the patogenicity of F. graminearum. At the same time, the effect of GMTs on the ability of rhinoceros to synthesise DON toxins was investigated and the results showed that the ability of ΔFgGmtB and ΔFgGmtA&B mutants to produce the DON toxin was significantly reduced, and the expression of toxin-related genes was also reduced.

20.
Behav Sci (Basel) ; 14(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38540521

RESUMO

Social trust is derived from the interaction of environmental and social factors, which has important significance for the sustainable development of society and social governance. In particular, in the post-pandemic era, tourist activity will receive special attention in terms of its role in the development of the public's social trust. On the basis of the sample of big data, this research takes China as an example to study the influences of different geographical and environmental elements on individuals' social trust as well as the common role played by the tourist activity. The research showed that the geographical environment and tourism activities have interacting effects on public social trust. This influencing mechanism is specifically manifested as the rice-growing ratio and tourist reception level can have interacting effects on the social trust of the residents in a tourist destination; pathogen stress and tourist supply level can exert interacting effects on the social trust of the residents in an area from which tourists originate; and economic development and tourist reception level can have interacting effects on the social trust of the residents in a tourist destination. By doing so, this research provides theoretical support and practical suggestions for the recovery of the public's social trust from the perspective of tourism geography in the post-pandemic era.

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