Gdp

The GTPase KRAS acts as a switch in cellular signaling, transitioning between inactive GDP-bound and active GTP-bound states. In about 20% of human cancers, oncogenic RAS mutations disrupt this balance, favoring the active form and promoting proliferative signaling, thus rendering KRAS an appealing target for precision medicine in oncology. In 2013, Shokat and co-workers achieved a groundbreaking feat by covalently targeting a previously undiscovered allosteric pocket (switch II pocket (SWIIP)) of KRASG12C ...

BACKGROUND: Interventions are needed to prevent and mitigate unhealthy commodity industry (UCI) influence on public health policy. Whilst literature on interventions is emerging, current conceptualisations remain incomplete as they lack considerations of the wider systemic complexities surrounding UCI influence, which may limit intervention effectiveness. This study applies systems thinking as a theoretical lens to help identify and explore how possible interventions relate to one another in the systems in which they are embedded...

Background Supportive periodontal care (SPC) is important in maintaining periodontal treatment outcomes. Hospital services provide specialist periodontal care at high costs. On completion of treatment, patients are discharged back to the general dental practitioner (GDP) to provide SPC. This project aimed to evaluate the change in GDPs' understanding of SPC over more than 20 years.Method A validated questionnaire about SPC was sent to GDPs during 1996 (397) and 2020 (300), with a response rate of 74% and 52%, respectively...

Activation of heterotrimeric G-proteins (Gαβγ) 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...

The µ-opioid receptor (µOR) is an important target for pain management1 and molecular understanding of drug action on µOR will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance and single-molecule fluorescence resonance energy transfer, how ligand-specific conformational changes of µOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several conformations of the cytoplasmic face of the receptor that interconvert on different timescales, including a pre-activated conformation that is capable of G-protein binding, and a fully activated conformation that markedly reduces GDP affinity within the ternary complex...

Alongside academic learning, there is increasing recognition that educational systems must also cater to students' well-being. This study examines the key factors that predict adolescent students' subjective well-being, indexed by life satisfaction, positive affect, and negative affect. Data from 522,836 secondary school students from 71 countries/regions across eight different cultural contexts were analyzed. Underpinned by Bronfenbrenner's bioecological theory, both machine learning (i.e., light gradient-boosting machine) and conventional statistics (i...

The Easterlin paradox questions the link between economic growth and national well-being, emphasizing the necessity to explore the impact of economic elasticity, income inequality, and their temporal and spatial heterogeneity on subjective happiness. Despite the importance of these factors, few studies have examined them together, thus ongoing debates about the impact of economics on well-being persist. To fill this gap, our analysis utilizes 11 years of panel data from 31 provinces in China, integrating macroeconomic indicators and social media content to reassess the Easterlin paradox...

Difucosyllactose (DFL) is a significant and plentiful oligosaccharide found in human breast milk. In this study, an artificial metabolic pathway of DFL was designed, focusing on the de novo biosynthesis of GDP-fucose from only glycerol. This was achieved by engineering Escherichia coli to endogenously overexpress genes manB , manC , gmd , and wcaG and heterologously overexpress a pair of fucosyltransferases to produce DFL from lactose. The introduction of α-1,2-fucosyltransferase from Helicobacter pylori (FucT2) along with α-1,3/4-fucosyltransferase (HP3/4FT) addressed rate-limiting challenges in enzymatic catalysis and allowed for highly efficient conversion of lactose into DFL...

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BACKGROUND: This study aims to expand on the concept of peace and health by drawing from Keynes' theory of the economic consequences of peace, in light of the global pandemic experienced in 2020 due to COVID_19. METHODS: In this paper, I will elaborate on the concept of 'security', as an indicator of peace in the time of biological shocks, in order to expand the definition of Keynesian precautionary motivation. This puts forth a new monetary policy model developed to make contributions to achieving global peace...

Social scientists have long debated the nature of cultural change in a modernizing and globalizing world. Some scholars predicted that national cultures would converge by adopting social values typical of Western democracies. Others predicted that cultural differences in values would persist or even increase over time. We test these competing predictions by analyzing survey data from 1981 to 2022 (n = 406,185) from 76 national cultures. We find evidence of global value divergence. Values emphasizing tolerance and self-expression have diverged most sharply, especially between high-income Western countries and the rest of the world...

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences...

Many children do not receive a full schedule of childhood vaccines, yet there is limited evidence on the cost-effectiveness of strategies for improving vaccination coverage. Evidence is even scarcer on the cost-effectiveness of strategies for reaching "zero-dose children," who have not received any routine vaccines. We evaluated the cost-effectiveness of periodic intensification of routine immunization (PIRI), a widely applied strategy for increasing vaccination coverage. We focused on Intensified Mission Indradhanush (IMI), a large-scale PIRI intervention implemented in India in 2017-2018...

Estimating the pollution loads in the Tuhai River is essential for developing a water quality standard scheme. This study utilized the improved output coefficient method to estimate the total pollution loads in the river basin while analyzing the influencing factors based on the STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) model. Findings indicated that the projected point source pollution loads for total phosphorus (TP), chemical oxygen demand (COD), and ammonia nitrogen (AN) would amount to 3937...

INTRODUCTION: Inequitable access to COVID-19 vaccines among countries is a pressing global health issue. Factors such as economic power, political power, political stability, and health system strength contribute to disparities in vaccine distribution. This study aims to assess the inequality in vaccine distribution among countries based on these factors and identify their relationship with COVID-19 vaccine distribution. METHODS: A Concentration Index (CI) analysis was conducted to evaluate inequalities in the distribution of COVID-19 vaccines among countries based on four separate variables: GDP per capita , political stability (PS), World Power Index (WPI), and Universal Health Coverage (UHC)...

BACKGROUND: The occurrence of thyroid cancer (TC) has increased in recent decades. Exposure to outdoor artificial light at night (ALN) is associated with an increased risk of cancer. AIM: To investigated the impact of ALN, as a significant environmental pollutant, on TC incidence worldwide. METHODS: The assessment involved analyzing satellite ALN data in conjunction with TC incidence data [adjusted standardized rate (ASR)], while considering the quality of cancer registries (QCR), gross domestic product (GDP) per person, and health expenditure per person (HEP) for each country...

AIMS: The effectiveness and cost-effectiveness of early intervention for psychosis (EIP) services are well established in high-income countries but not in low- and middle-income countries (LMICs). Despite the scarcity of local evidence, several EIP services have been implemented in LMICs. Local evaluations are warranted before adopting speciality models of care in LMICs. We aimed to estimate the cost-effectiveness of implementing EIP services in Brazil. METHODS: A model-based economic evaluation of EIP services was conducted from the Brazilian healthcare system perspective...

Small GTPase is a type of crucial regulator in eukaryotes. It acts as a molecular switch by binding with GTP and GDP in cytoplasm, affecting various cellular processes. Small GTPase were divided into five subfamilies based on sequence, structure and function: Ras, Rho, Rab, Arf/Sar and Ran, with Rab being the largest subfamily. Members of the Rab subfamily play an important role in regulating complex vesicle transport and microtubule system activity. Plant cells are composed of various membrane-bound organelles, and vesicle trafficking is fundamental to the existence of plants...

The ADP-ribosylation factors (Arfs) constitute a family of small GTPases within the Ras superfamily, with a distinguishing structural feature of a hypervariable N-terminal extension of the G domain modified with myristate. Arf proteins, including Arf1, have roles in membrane trafficking and cytoskeletal dynamics. While screening for Arf1:small molecule co-crystals, we serendipitously solved the crystal structure of the non-myristoylated engineered mutation [L8K]Arf1 in complex with a GDP analogue. Like wild-type (WT) non-myristoylated Arf1•GDP, we observed that [L8K]Arf1 exhibited an N-terminal helix that occludes the hydrophobic cavity that is occupied by the myristoyl group in the GDP-bound state of the native protein...

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...