Regulatory Control Research Articles

Evaluating Nuclear Forensic Signatures for Advanced Reactor Deployment: A Research Priority Assessment

The development and deployment of a new generation of nuclear reactors necessitates a thorough evaluation of techniques used to characterize nuclear materials for nuclear forensic applications. Advanced fuels proposed for use in these reactors present both challenges and opportunities for the nuclear forensic field. Many efforts in pre-detonation nuclear forensics are currently focused on the analysis of uranium oxides, uranium ore concentrates, and fuel pellets since these materials have historically been found outside of regulatory control. The increasing use of TRISO particles, metal fuels, molten fuel salts, and novel ceramic fuels will require an expansion of the current nuclear forensic suite of signatures to accommodate the different physical dimensions, chemical compositions, and material properties of these advanced fuel forms. In this work, a semi-quantitative priority scoring system is introduced to identify the order in which the nuclear forensics community should pursue research and development on material signatures for advanced reactor designs. This scoring system was applied to propose the following priority ranking of six major advanced reactor categories: (1) molten salt reactor (MSR), (2) liquid metal-cooled reactor (LMR), (3) very-high-temperature reactor (VHTR), (4) fluoride-salt-cooled high-temperature reactor (FHR), (5) gas-cooled fast reactor (GFR), and (6) supercritical water-cooled reactor (SWCR).

Institutional Challenges and Continuous Pending on Levying Excise on the Use of Plastics in Indonesia

In response to the mounting plastic waste issue, the Indonesian government has introduced various measures aimed at curbing plastic usage, but these initiatives have fallen short in altering public behavior. A more impactful strategy would involve implementing a disincentive by levying additional fees on plastic use, effectively increasing its cost. Discussions on a plastic excise were initiated between the Indonesian government and the House of Representatives but have since stalled. This study aims to higlight the necessity of a plastic excise in regulating the behavior of Indonesian citizens and explores the appropriate methods for the government to formulate such an excise policy. A qualitative research method was employed, utilizing thorough interviews and extensive literature review. Findings suggest that the environmental damage inflicted by plastic waste justifies its classification as taxable goods, warranting regulatory control over its consumption due to the adverse effects on society and ecology. These findings serve as the foundation for the government to consider a plastic excise. The challenge lies in identifying the specific plastic types to be taxed, necessitating renewed coordination and dialogue with the pertinent Ministries and Agencies within the Inter-Ministerial Committee. This is essential to gain the Indonesian House of Representatives' approval and to address the complexities in policy formulation, considering that state levies shall be approved by the parliement. A possible solution to this challenge is to synchronize the taxable goods' plastic types with those outlined in the existing regulations of the Waste Reduction Roadmap by Producers, ensuring consistency and regulatory alignment.

Multi-organ gene expression analysis and network modeling reveal regulatory control cascades during the development of hypertension in female spontaneously hypertensive rat.

Hypertension is a multifactorial disease with stage-specific gene expression changes occurring in multiple organs over time. The temporal sequence and the extent of gene regulatory network changes occurring across organs during the development of hypertension remain unresolved. In this study, female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were used to analyze expression patterns of 96 genes spanning inflammatory, metabolic, sympathetic, fibrotic, and renin-angiotensin (RAS) pathways in five organs, at five time points from the onset to established hypertension. We analyzed this multi-dimensional dataset containing ~15,000 data points and developed a data-driven dynamic network model that accounts for gene regulatory influences within and across visceral organs and multiple brainstem autonomic control regions. We integrated the data from female SHR and WKY with published multiorgan gene expression data from male SHR and WKY. In female SHR, catecholaminergic processes in the adrenal gland showed the earliest gene expression changes prior to inflammation-related gene expression changes in the kidney and liver. Hypertension pathogenesis in male SHR instead manifested early as catecholaminergic gene expression changes in brainstem and kidney, followed by an upregulation of inflammation-related genes in liver. RAS-related gene expression from the kidney-liver-lung axis was downregulated and intra-adrenal RAS was upregulated in female SHR, whereas the opposite pattern of gene regulation was observed in male SHR. We identified disease-specific and sex-specific differences in regulatory interactions within and across organs. The inferred multi-organ network model suggests a diminished influence of central autonomic neural circuits over multi-organ gene expression changes in female SHR. Our results point to the gene regulatory influence of the adrenal gland on spleen in female SHR, as compared to brainstem influence on kidney in male SHR. Our integrated molecular profiling and network modeling identified a stage-specific, sex-dependent, multi-organ cascade of gene regulation during the development of hypertension.

Exploring the clinical potential of circulating LncRNAs in breast cancer: insights into primary signaling pathways and therapeutic interventions.

Breast cancer (BC) occupies the top spot among women on a global scale. The tumor has a significant degree of heterogeneity, displaying a notable prevalence of medication resistance, recurrence, and metastasis, rendering it one of the most lethal forms of malignant neoplasms. The timely identification, ongoing evaluation of therapeutic interventions, and accurate prediction of outcomes play crucial roles in determining the overall survival rates of women with BC. Nevertheless, the absence of precise biomarkers remains a significant determinant impacting the overall well-being and both the physical and emotional health of BC patients. Long noncoding RNA (lncRNA) exerts regulatory control over several genes and signaling pathways, hence assuming crucial roles in the development of neoplastic growth. Recently, research has indicated that the atypical expression of circulating lncRNAs in various biological bodily fluids has a noteworthy impact on the early detection, pathological categorization, staging, monitoring of therapy outcomes, and evaluation of prognosis in cases of BC. This article aims to assess the potential clinical utility of circulating lncRNAs in the context of BC focusing on specific primary signaling pathways; Wnt/β-catenin, Notch, TGF-β, and hedgehog (Hh), in addition to some therapeutic interventions.

Neurodevelopment in the First 2 Years of Life Following Prenatal Exposure to Maternal SARS-CoV-2 Infection

The effects of prenatal exposure to SARS-CoV-2 infection on child development throughout the first 2 years of life are unknown. To evaluate whether prenatal exposure to SARS-CoV-2 infection was associated with child neurodevelopmental outcomes during the first 2 years of life. This cohort study used data from the longitudinal, population-based pan-Canadian Pregnancy During the COVID-19 Pandemic cohort, which recruited participants from April 2020 to July 2022. Children were categorized as exposed to prenatal SARS-CoV-2 infection if their birthing parent had a positive polymerase chain reaction test performed by a health authority or as a healthy negative comparison if their birthing parent did not have SARS-CoV-2 antibodies in their postpartum dried blood spot sample. Prenatal SARS-CoV-2 infection. The birthing parent reported on their child's temperament at ages 6 and 24 months, developmental milestones at ages 12 and 24 months, and social-emotional milestones at ages 12 and 24 months. A total of 896 children were included, with 96 children who had been exposed to a prenatal SARS-CoV-2 infection (mean [SD] gestational age at birth, 39.20 [1.50] weeks; 45 [47%] male) and 800 were healthy negative comparisons (mean [SD] gestational age at birth, 39.47 [1.54] weeks; 388 [49%] male). In analyses of covariance adjusted for prepregnancy medical conditions and household socioeconomic status, prenatal exposure to SARS CoV-2 infection was associated with slightly higher regulatory control scores, indicating more regulation, at age 6 months (difference in means, 0.19 [95% CI, 0.02-0.36]; P = .03; ηp2 = 0.01). No significant differences were observed for the other neurodevelopmental outcomes. In mixed models adjusted for the same covariates that aimed to examine change in outcomes over time, prenatal SARS-CoV-2 infection exposure was not associated with developmental change in any neurodevelopmental outcomes between ages 6 and 24 months. In this longitudinal cohort study of multiple aspects of child neurodevelopment between ages 6 and 24 months, negligible associations between prenatal exposure to SARS-CoV-2 infection and child outcomes were observed. Follow-up research is warranted to determine whether these predominantly null effects persist into later childhood.

Amend the Mental Health Care Act 2017: A Survey of Indian psychiatrists (Part 2)

Background: Information about the experience of practicing psychiatrists with the use of the Mental Health Care Act (MHCA), 2017, India, after 5 years of its promulgation has not been available. Aim: The present study was carried out to understand the experience of the practicing psychiatrists in using and complying with the MHCA 2017 and to bring out the problems and suggested reforms, if any, in various provisions of the MHCA 2017. Methods: An online survey by practicing psychiatrists of Indian Psychiatric Society on the various sections and provisions of the MHCA 17 was carried out through structured and open-ended responses. This paper presents the qualitative analysis of the open-ended responses. Results: There were 600 respondents, who gave a total of 1239 (range 116–154) responses to eight open-ended questions about various provisions of the MHCA. Qualitative analysis revealed that most respondents opined for keeping the General Hospital Psychiatry units exempted from inclusion as the mental health establishment, thus treating physical illness at par with the mental illness; a separate stand-alone law for mental illness perpetuates stigma, asked for a larger representation of psychiatrists in the State Mental Health Authority and Mental Health Review Boards. Most respondents opined that the provisions of capacity assessment, nominated representative, and advance directive are a hinderance in treatment and should be amended; treating psychiatrists and family/caregiver’s consent should suffice for supported admission, just like in other disciplines of medicine; and MHCA 2017 needs major amendments/repeal to make it convenient for patient care. Any unauthorized places/centers where persons with mental illness are kept should come under regulatory control of the state mental health authorities. Conclusion The survey has highlighted several deficiencies and operational difficulties in the current Act that hinder the delivery of mental health care to patients with mental illness in the country and need amendments.

Dorsal fin height is not an effective tool to distinguish hatchery and wild steelhead in the field

AbstractObjectiveTo maximize harvest of hatchery steelhead Oncorhynchus mykiss and Pacific salmon Oncorhynchus spp. while reducing impacts to wild conspecifics, fishery managers rely on the ability of anglers to distinguish between the two. Fin erosion, including dorsal fin erosion, is a common result of hatchery rearing of juvenile salmonids. Since the 1980s, managers in the Pacific Northwest have utilized adult steelhead dorsal fin height as a regulatory control rule, requiring anglers to release steelhead with dorsal fins over a height threshold. This approach assumes that all or most hatchery fish have shorter dorsal fins than their wild counterparts. This study was designed to test this assumption.MethodsWe compared steelhead origin (hatchery or wild) determined using scale analysis and adipose fin clipping (hatchery n = 127, wild n = 71) with origin estimated using dorsal fin height.ResultOverall, a static dorsal fin height threshold (2.25 in, 5.72 cm) correctly identified 90% of hatchery‐origin steelhead but misidentified nearly half (44%) of wild fish as hatchery. Dorsal fin height of known hatchery fish correlated with fish length, indicating a weakness of using a static dorsal height threshold as a management tool. The accuracy of distinguishing wild fish improved, but only marginally (56–76%), using a classification model where dorsal fin height of known origin fish from this study was a continuous predictor of origin. In comparison, adipose fin status correctly identified 97% of unmarked fish as wild.ConclusionThe low accuracy of the classification model and static dorsal fin height thresholds at distinguishing hatchery and wild steelhead due to a strong correlation between dorsal fin height and fork length and the high fork length variability of hatchery origin fish. Given the low cost and accuracy of adipose fin clipping and the potentially high conservation risk associated with misidentification, we recommend discontinuing the use of dorsal fin height as a harvest control rule for steelhead.

The prognostic significance of twist in pancreatic cancer and its role in cancer promotion through the regulation of the immune microenvironment and EMT mechanisms

ObjectivePancreatic cancer has a poor prognosis due to its high malignancy and rapid progression. The limited immunogenicity of pancreatic cancer (PAAD) contributes to its low responsiveness to immunotherapy, yet its underlying mechanism remains poorly understood. As a cancer promoting gene, Twist participates in EMT in various tumors and promotes tumor progression. The interplay between EMT and the tumor microenvironment (TME) emerges as a pivotal factor influencing tumor immunity and response to immunotherapy. Twist therefore has potential as a biomarker for gauging the outcome of tumour immunotherapy.This research aimed to assess the Twist's prognostic significance in PAAD and its relationship to immunotherapy response.MethodsIn this research, transcriptional data and epigenetic alterations of Twist in pancreatic cancer, along with their impact on the prognosis of PAAD patients, were analyzed using databases. Functional enrichment analysis elucidated the biological role of Twist in PAAD. Subsequently, databases including CIBERSORT and TIDE were employed to investigate the association between Twist expression and immune cell infiltration, immune checkpoint genes, and immunotherapy sensitivity within the pancreatic cancer immune microenvironment.Paraffinized specimens from patients with pancreatic ductal adenocarcinoma confirmed by postoperative pathology were selected for Twist expression verification, and the difference was analyzed by Chi-square test; uncontaminated pancreatic cancer cell lines were used for Twist expression verification, and the differences were analyzed by Student t-test.ResultsTwist mRNA expression was notably upregulated in PAAD, positively correlating with gene methylation levels. Analyses of Kaplan–Meier and Cox regression showed a correlation between better overall survival and lower Twist expression. Functional annotation indicated that Twist-associated differentially expressed genes (DEGs) were involved in EMT regulation and acute inflammation. High expression of Twist leads to a significant reduction in the infiltration of anti-tumor immune cells such as Monocytes, NKcellsactivated, and TcellsCD8, further supporting its creation of a typical immunosuppressive microenvironment in pancreatic cancer. Twist expression is positively correlated with the expression of HARVCR2, LAIR1, LGALS3 and other genes, which may be related to the treatment response to immune checkpoint inhibitors (ICIs). TIDE analysis predicts that patients with high expression of Twist will be insensitive to immunotherapy. Twist is significantly over-expressed in pancreatic cancer cell lines and tissues, and is negatively correlated with E-cadhrin expression, but positively correlated with N-cadherin,Snail, and ZEB1.ConclusionHigh Twist expression in PAAD signifies a grim prognosis. Its elevated levels not only contribute to tumor progression through EMT induction but also exert regulatory control over the immune microenvironment, leading to immunosuppression and diminished effectiveness of immunotherapy.

Global regulator AdpA directly binds to tunicamycin gene cluster and negatively regulates tunicamycin biosynthesis in Streptomyces clavuligerus.

Since a transcriptional regulator has yet to be identified within the tunicamycin biosynthetic gene cluster in Streptomyces clavuligerus, we conducted a comprehensive investigation by focusing on the possible function of the pleiotropic regulator AdpA on tunicamycin. The genes encoding early steps of tunicamycin biosynthesis were significantly upregulated in S. clavuligerus ΔadpA. At the same time, they were downregulated in adpA overexpressed strain as shown by RNA-sequencing (RNA-seq) and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis. The tunicamycin gene cluster's co-transcription pattern was understood by reverse transcriptase polymerase chain reaction (RT-PCR). Our Electrophoretic Mobility Shift Assay (EMSA) data clearly showed AdpA's binding to the upstream sequence of the tunA gene, asserting its regulatory control. In addition to its direct negative regulation of tunicamycin biosynthesis, AdpA operates at a global level by orchestrating various regulatory genes in S. clavuligerus, such as wblA, whiB, bldM, arpA, brp, and adsA involved in morphological differentiation and secondary metabolite biosynthesis as depicted in RNA-seq data. This study represents a significant milestone by unveiling the AdpA regulator's pathway-specific and global regulatory effect in S. clavuligerus.

Scalable identification of lineage-specific gene regulatory networks from metacells with NetID

The identification of gene regulatory networks (GRNs) is crucial for understanding cellular differentiation. Single-cell RNA sequencing data encode gene-level covariations at high resolution, yet data sparsity and high dimensionality hamper accurate and scalable GRN reconstruction. To overcome these challenges, we introduce NetID leveraging homogenous metacells while avoiding spurious gene–gene correlations. Benchmarking demonstrates superior performance of NetID compared to imputation-based methods. By incorporating cell fate probability information, NetID facilitates the prediction of lineage-specific GRNs and recovers known network motifs governing bone marrow hematopoiesis, making it a powerful toolkit for deciphering gene regulatory control of cellular differentiation from large-scale single-cell transcriptome data.

Deep learning-based enhancement of fluorescence labeling for accurate cell lineage tracing during embryogenesis.

Automated cell lineage tracing throughout embryogenesis plays a key role in the study of regulatory control of cell fate differentiation, morphogenesis and organogenesis in the development of animals, including nematode Caenorhabditis elegans. However, automated cell lineage tracing suffers from an exponential increase in errors at late embryo because of the dense distribution of cells, relatively low signal-to-noise ratio (SNR) and imbalanced intensity profiles of fluorescence images, which demands a huge amount of human effort to manually correct the errors. The existing image enhancement methods are not sensitive enough to deal with the challenges posed by the crowdedness and low signal-to-noise ratio. An alternative method is urgently needed to assist the existing detection methods in improving their detection and tracing accuracy, thereby reducing the huge burden for manual curation. We developed a new method, termed as DELICATE, that dramatically improves the accuracy of automated cell lineage tracing especially during the stage post 350 cells of C. elegans embryo. DELICATE works by increasing the local SNR and improving the evenness of nuclei fluorescence intensity across cells especially in the late embryos. The method both dramatically reduces the segmentation errors by StarryNite and the time required for manually correcting tracing errors up to 550-cell stage, allowing the generation of accurate cell lineage at large-scale with a user-friendly software/interface. All images and data are available at https://doi.org/10.6084/m9.figshare.26778475.v1. The code and user-friendly software are available at https://github.com/plcx/NucApp-develop.

Psychological Determinants of Health Behavior.

This review provides a critical overview of current evidence on psychological health behavior determinants and its value in informing intervention and future determinants research. The review begins with work labeling and classifying the myriads of determinants available in the extant research to arrive at core groups of determinants. Next, the conceptual bases of these determinant groups are identified, and the weight of the evidence for their purported effects on health behavior, including belief-based determinants (e.g., outcome expectancies, capacity beliefs), determinants representing self-regulatory capacity (e.g., planning, action control) and nonconscious processes (e.g., habit, implicit cognition), and dispositional determinants (e.g., personality, regulatory control), is critically evaluated. The review also focuses on the theory-based mechanisms underpinning determinant effects and moderating conditions that magnify or diminish them. Finally, the review recommends a shift away from research on determinants as correlates, outlines how determinants can inform intervention development and mechanisms of action tests, suggests alternatives to predominant individualist approaches, and proposes future research directions.

Challenges of Conducting Point-Of-Care Testing Operations In The Municipal Public Health System Based Ambulatory Care Clinics In New York City

Abstract Introduction/Objective Our New York City Municipal Public Health System- based multisite ambulatory clinics that offer various waived POCT (point of care tests) and provider-performed microscopy (PPM) to our communities, ensure standardization and quality of POC testing across our health system. Our laboratory service conducts system-wide centralized implementation, monitoring and oversight of the POCT operations regarding regulatory compliance, test performance, quality control and training. With our day-to-day POCT operations, like all other clinical laboratories, our ambulatory care clinics encounter various hurdles and challenges. Here we elaborated on the issues we encounter and how we manage to overcome them. Methods/Case Report We identified and stratified the challenges that affect our managerial as well as field-level laboratory operations and devised ways to deal with those POCT operational issues. Results (if a Case Study enter NA) Among the staffing issues, rapid staff turnover causes significant delays or cessation of POCT operations in our ambulatory care clinics, due to orientation, re-education and ensuring competency to the staff, that conducts POCT in our clinics. Besides, supply shortages, staff shortages and absences due to illness and overwork are the issues, noted at the laboratory field operational level. Delays in the processing of paperwork and new staff recruitments and in the laboratory supply chains are notable management issues. Conclusion Even though the vastness and complexity of our multisite ambulatory care network sometimes affect our ambulatory care clinic POCT operation in various challenging way, our timely, planned and coordinated intervention, close monitoring and communication and rapid initiatives handle those issues very effectively to ensure the quality of POC testing for the patient safety and care across our health system, which is one of the largest municipal-based public health care, in the country.

Can a regulatory control network be used for a territorial monitoring of antimicrobial resistance in water intended for human consumption?

Antimicrobial resistance genes and resistant bacteria could be found in water intended for human consumption (WIHC). In France, although the microbiological quality of WIHC is strictly monitored, antimicrobial resistance is not. The aim of this study is to test the concept of the use of the regulatory surveillance of WIHC to monitor antimicrobial resistance in a French area.Based on 2211 Petri dishes seeded for regulatory enumeration of Escherichia coli, that corresponds to sanitary surveillance of 2 French departments from January to April 2021, we characterized phenotypic and genotypic resistance of isolated E. coli strains. blaTEM, blaSHV, blaCTX-M that are the most frequent beta-lactamases-encoding genes in human infections were also researched on cultivable Gram negative-community.

A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival

Approximately a quarter of the human genome consists of gene deserts, large regions devoid of genes often located adjacent to developmental genes and thought to contribute to their regulation. However, defining the regulatory functions embedded within these deserts is challenging due to their large size. Here, we explore the cis-regulatory architecture of a gene desert flanking the Shox2 gene, which encodes a transcription factor indispensable for proximal limb, craniofacial, and cardiac pacemaker development. We identify the gene desert as a regulatory hub containing more than 15 distinct enhancers recapitulating anatomical subdomains of Shox2 expression. Ablation of the gene desert leads to embryonic lethality due to Shox2 depletion in the cardiac sinus venosus, caused in part by the loss of a specific distal enhancer. The gene desert is also required for stylopod morphogenesis, mediated via distributed proximal limb enhancers. In summary, our study establishes a multi-layered role of the Shox2 gene desert in orchestrating pleiotropic developmental expression through modular arrangement and coordinated dynamics of tissue-specific enhancers.

Mechanisms of tamoxifen resistance: insight from long non-coding RNAs.

Breast cancer(BC) is the second most prevalent tumor in the world and one of the most lethal tumors in women. Patients with estrogen receptor-positive breast cancer can obtain significant advantages from endocrine therapies including tamoxifen, aromatase inhibitors, and others. However, the development of primary or acquired drug resistance ultimately leads to discontinuation of treatment with adverse consequences for breast cancer patients, and the underlying mechanisms have not been fully elucidated. Long non-coding RNAs (lncRNAs) play pivotal roles in orchestrating fundamental biochemical and cellular processes. They exert regulatory control over various processes including epigenetics, gene transcription, post-transcriptional modifications, and translation. Additionally, they influence key biological events like cell cycle progression, cell differentiation, and development. For the past few years, the relationship between lncRNAs and endocrine resistance has gained increasing attention, leading to a surge in related studies. LncRNAs mediate tamoxifen resistance in cancer by utilizing a variety of molecular mechanisms, including enhanced estrogen receptor (ER) signaling, inhibition of apoptosis, autophagy, exosome-mediated transfer, epigenetic alterations, epithelial-to-mesenchymal transition, and acting as competitive endogenous RNAs(ceRNAs). In this comprehensive review, we systematically summarize the critical role and intricate molecular mechanisms by which lncRNAs influence the development of tamoxifen resistance in breast cancer. Furthermore, we propose the potential clinical significance of lncRNAs as innovative therapeutic targets and prognostic biomarkers for breast cancer.

Unveiling the Complexity of cis-Regulation Mechanisms in Kinases: A Comprehensive Analysis.

Protein cis-regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis. To accomplish this, we curated an extensive dataset of kinases featuring annotated CREs, organized into homolog families through multiple sequence alignments. Key molecular attributes, including disorder and secondary structure content, active and ATP-binding sites, post-translational modifications, and disease-associated mutations, were systematically mapped onto all sequences. Additionally, we explored the potential for conformational changes between active and inactive states. Finally, we explored the presence of these kinases within membraneless organelles and elucidated their functional roles therein. CREs display a continuum of structures, ranging from short disordered stretches to fully folded domains. The adaptability demonstrated by CREs in achieving the common goal of kinase inhibition spans from direct autoinhibitory interaction with the active site within the kinase domain, to CREs binding to an alternative site, inducing allosteric regulation revealing distinct types of inhibitory mechanisms, which we exemplify by archetypical representative systems. While this study provides a systematic approach to comprehend kinase CREs, further experimental investigations are imperative to unravel the complexity within distinct kinase families. The insights gleaned from this research lay the foundation for future studies aiming to decipher the molecular basis of kinase dysregulation, and explore potential therapeutic interventions.

MAT2B regulates the protein level of MAT2A to preserve RNA N6-methyladenosine

MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP+-dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP+ remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP+ with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP+. Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.

IMPACT OF DIGITALISATION ON BANKING SECTOR

The banking sector has been substantially changed by the fast development of digital technology. The effect of digitalisation on general financial services, client contacts, and banking operations is investigated in this article. In banking, digitalisation has brought about the automation of formerly manual procedures, therefore improving client happiness, efficiency, and operating expenses while lowering running costs. Offering 24/7 access to financial services from anywhere in the globe, services such internet banking, smartphone apps, and digital payment systems have transformed the way consumers connect with banks. Furthermore, digitalisation has helped fintech to emerge, therefore undermining established banking structures and encouraging more innovation and competitiveness. Advanced technologies such artificial intelligence (AI), machine learning (ML), and blockchain have been embraced by banks to guarantee better security in transactions, provide tailored services, and help to guide decisions. Although digitalisation has many advantages, it also brings problems like cybersecurity threats, data privacy issues, and the necessity of large technological infrastructure investment. This study also addresses its function in financial inclusion by enabling underprivileged groups to use banking services. Banks have to strike a mix between innovation and regulatory compliance, risk control, and client confidence as the digital revolution unfolds. The results of this research imply that banks must embrace digital transformation if they are to stay competitive in an economy becoming more and more digital and also meet the changing demands of tech-savvy customers.

FINANCIAL CRISIS AND INSTABILITY

Financial crises and instability are common occurrences in the world economy, and they have significant effects on both developed and developing nations. The numerous causes of financial crises and the ensuing instability in the financial markets are thoroughly examined. It explains the theoretical foundations of financial crises, going over important ideas including market bubbles, excessive leverage, and regulatory shortcomings The paper also looks into how regulations and governmental actions can either exacerbate or lessen financial crises, how financial institutions contribute to systemic risk propagation and how interconnected they are. It looks at how the spread of crises across borders and asset classes can aggravate their severity through the contagion effect. It also covers the socio-economic fallout from financial crises, such as social unrest, income inequality, and unemployment. The summary concludes by highlighting how crucial it is to have strong regulatory control and proactive risk management to avert and lessen future financial disasters. It promotes a comprehensive strategy that blends international collaboration, regulatory changes, and responsible risk-taking to promote long-term economic growth and stability in a global financial system that is becoming more linked.