Consequences Of Regulation Research Articles

A Suite of Foundation Models Captures the Contextual Interplay Between Codons.

In the canonical genetic code, many amino acids are assigned more than one codon. Work by us and others has shown that the choice of these synonymous codon is not random, and carries regulatory and functional consequences. Existing protein foundation models ignore this context-dependent role of coding sequence in shaping the protein landscape of the cell. To address this gap, we introduce cdsFM, a suite of codon-resolution large language models, including both EnCodon and DeCodon models, with up to 1B parameters. Pre-trained on 60 million protein-coding sequences from more than 5,000 species, our models effectively learn the relationship between codons and amino acids, recapitualing the overall structure of the genetic code. In addition to outperforming state-of-the-art genomic foundation models in a variety of zero-shot and few-shot learning tasks, the larger pre-trained models were superior in predicting the choice of synonymous codons. To systematically assess the impact of synonymous codon choices on protein expression and our models' ability to capture these effects, we generated a large dataset measuring overall and surface expression levels of three proteins as a function of changes in their synonymous codons. We showed that our EnCodon models could be readily fine-tuned to predict the contextual consequences of synonymous codon choices. Armed with this knowledge, we applied EnCodon to existing clinical datasets of synonymous variants, and we identified a large number of synonymous codons that are likely pathogenic, several of which we experimentally confirmed in a cell-based model. Together, our findings establish the cdsFM suite as a powerful tool for decoding the complex functional grammar underlying the choice of synonymous codons.

Issues of Cyber security and its solutions in Nepalese Context

In today's digital age, the internet's expansion has brought great convenience but also raised cyber threats. So, identify the issue of cyber-security and its solution in Nepalese context is significant. Descriptive design and qualitative methods were employed, with data sourced from Google Scholar and analyzed through thematic analysis. The study shows a myriad of issues stemming from inadequate cyber security awareness in Nepal, including increased vulnerability to cyber-attacks, data breaches, and societal, economic, and regulatory consequences. Bridging the gap in cyber security awareness is imperative to mitigate risks effectively and foster a secure digital environment in Nepal. Strategies emphasizing education, training, and regulatory frameworks are vital for addressing these challenges and promoting technological advancement and societal trust. This study proposes AI-driven solutions to address the lack of cyber security awareness in the Nepalese context, offering a unique approach to mitigate cyber threats and foster a secure digital environment.

Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.

Ferritin, as an iron storage protein, has the potential to inhibit ferroptosis by reducing excess intracellular free iron concentrations and lipid reactive oxygen species (ROS). An insufficient amount of ferritin is one of the conditions that can lead to ferroptosis through the Fenton reaction mediated by ferrous iron. Consequently, upregulation of ferritin at the transcriptional or posttranscriptional level may inhibit ferroptosis. In this review, we have discussed the essential role of ferritin in ferroptosis and the regulatory mechanism of ferroptosis in ferritin-deficient individuals. The description of the regulatory factors governing ferritin and its properties in regulating ferroptosis as underlying mechanisms for the pathologies of diseases will allow potential therapeutic approaches to be developed.

Translational Regulation of Duplicated Gene Expression Evolution in Allopolyploid Cotton.

Polyploidy, a prevalent event in plant evolution, drives phenotypic diversification and speciation. While transcriptional changes and regulation in polyploids have been extensively studied, the translational level impact remains largely unexplored. To address this gap, we conducted a comparative transcriptomic and translatomic analysis of cotton leaves from allopolyploid species G. hirsutum (AD1) and G. barbadense (AD2) relative to their model A-genome and D-genome diploid progenitors. Our data revealed that while allopolyploidization significantly affects the transcriptional landscape, its impact on translation was relatively modest, evidenced by a narrower expression range and fewer expression changes in ribosome-protected fragments than in mRNA levels. Allopolyploid-specific changes commonly identified in both AD1 and AD2 were observed in 7393 genes at either transcriptional or translational levels. Interestingly, the majority of translational changes exhibited concordant down-regulation in both ribosome-protected fragments and mRNA, particularly associated with terpenoid synthesis and metabolism (352 genes). Regarding translational efficiency (TE), at least one-fifth of cotton genes exhibit translational level regulation, with a general trend of more down-regulation (13.9-15.1%) than up-regulation (7.3-11.2%) of TE. The magnitude of translational regulation was slightly reduced in allopolyploids compared with diploids, and allopolyploidy tends to have a more profound impact on genes and functional associations with ultra-low TE. Moreover, we demonstrated a reduced extent of homeolog expression biases during translation compared with transcription. Our study provides insights into the regulatory consequences of allopolyploidy post-transcription, contributing to a comprehensive understanding of regulatory mechanisms of duplicated gene expression evolution.

Alleviation of Antarctic krill oil on dextran sulfate sodium exposure induced chronic ulcerative colitis and depressive-like behavior

Substantial evidence indicate that Antarctic krill oil (KO) is an effective method for alleviating acute ulcerative colitis (UC). Nevertheless, UC is a chronic disease, and the chronic colitis model is more conducive to simulating its pathological characteristics. The objective of this study was to establish a chronic UC model in C57BL/6 mice and identify the regulatory consequences and feasible mechanisms of KO on chronic UC and its associated depressive-like behaviors. The results showed that KO alleviated the pathological features of UC and depression-like behavior. Further mechanisms suggested that KO significantly suppressed gut-brain inflammation, increased the concentration of 5-hydroxytryptamine (5-HT) and the expression of postsynaptic density protein 95 (PSD95) and brain-derived neurotrophic factor (BDNF), protected the integrity of the gut barrier and blood–brain barrier. Moreover, KO maintained the equilibrium of the intestinal flora. The findings suggested that KO may be a promising approach for alleviating UC and its concomitant psychiatric disorders.

Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots.

The classical pathway of the complement system is activated by the binding of C1q in the C1 complex to the target activator, including immune complexes. Factor H is regarded as the key downregulatory protein of the complement alternative pathway. However, both C1q and factor H bind to target surfaces via charge distribution patterns. For a few targets, C1q and factor H compete for binding to common or overlapping sites. Factor H, therefore, can effectively regulate the classical pathway activation through such targets, in addition to its previously characterized role in the alternative pathway. Both C1q and factor H are known to recognize foreign or altered-self materials, e.g., bacteria, viruses, and apoptotic/necrotic cells. Clots, formed by the coagulation system, are an example of altered self. Factor H is present abundantly in platelets and is a well-known substrate for FXIIIa. Here, we investigated whether clots activate the complement classical pathway and whether this is regulated by factor H. We show here that both C1q and factor H bind to the fibrin formed in microtiter plates and the fibrin clots formed under in vitro physiological conditions. Both C1q and factor H become covalently bound to fibrin clots, and this is mediated via FXIIIa. We also show that fibrin clots activate the classical pathway of complement, as demonstrated by C4 consumption and membrane attack complex detection assays. Thus, factor H downregulates the activation of the classical pathway induced by fibrin clots. These results elucidate the intricate molecular mechanisms through which the complement and coagulation pathways intersect and have regulatory consequences.

INTERNATIONAL FINANCIAL REPOTING STANDARDS & IT’S CONVERGENCE IN INDIA 1.

In order to improve financial statemet comparability, accountability, and transparency, the adoption and convergence of International Financial Reporting Standards (IFRS) have become essential components of financial reporting on a global scale. This study examines the development and effects of IFRS convergence in India, focusing on the corporate, regulatory, and financial ecosystem consequences. Financial reporting procedures have undergone major changes as a result of the gradual implementation of the Indian Accounting Standards (Ind AS), which are convergent with IFRS, across a number of sectors. The present study scrutinizes the advantages of implementing IFRS, such as enhanced investor trust and global comparability, in conjunction with the obstacles encountered by Indian enterprises, such as escalated compliance expenses and the intricacy of novel standards. The study also explores the role regulatory organizations play in promoting the convergence process, including the Securities and Exchange Board of India (SEBI) and the Institute of Chartered Accountants of India (ICAI). This study offers insights into the efficacy of IFRS convergence in India by a thorough analysis of the body of research, case studies, and empirical data. It highlights significant areas of success as well as persistent challenges. The results indicate that although convergence has helped India's standing in the international financial sphere, ongoing work is still needed to resolve implementation problems and guarantee the smooth adoption of IFRS in the Indian setting. Keywords: Finance, Financial Report, IFRS.

Alternative 3′UTR expression induced by T cell activation is regulated in a temporal and signal dependent manner

The length of 3′ untranslated regions (3′UTR) is highly regulated during many transitions in cell state, including T cell activation, through the process of alternative polyadenylation (APA). However, the regulatory mechanisms and functional consequences of APA remain largely unexplored. Here we present a detailed analysis of the temporal and condition-specific regulation of APA following activation of primary human CD4+ T cells. We find that global APA changes are regulated temporally and CD28 costimulatory signals enhance a subset of these changes. Most APA changes upon T cell activation involve 3′UTR shortening, although a set of genes enriched for function in the mTOR pathway exhibit 3′UTR lengthening. While upregulation of the core polyadenylation machinery likely induces 3′UTR shortening following prolonged T cell stimulation; a significant program of APA changes occur prior to cellular proliferation or upregulation of the APA machinery. Motif analysis suggests that at least a subset of these early changes in APA are driven by upregulation of RBM3, an RNA-binding protein which competes with the APA machinery for binding. Together this work expands our understanding of the impact and mechanisms of APA in response to T cell activation and suggests new mechanisms by which APA may be regulated.

HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription

Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.

From securities to currencies: the regulatory consequences of adopting cryptocurrencies as legal tender

ABSTRACT In 2021, El Salvador designated Bitcoin as legal tender within that country, payable for all debts, public and private. The move is novel in the realm of cryptocurrency regulation, but fits within a time-honoured battle over monetary policy with which every country engages. This piece examines the impacts of legal tender designations in these various areas and maps the current regulatory framework of cryptocurrency transactions, to argue that cryptocurrency’s practical uses are decoupling states from monetary control and developing a transnational legal theory agnostic to concerns such as the legal tender question. It shows how the El Salvador regulation threatens to shift the dominant global economic regime towards a world wherein money may not be governed by states at all. The paper develops this transnational legal theory through mapping the US regulatory framework regarding cryptocurrency and examining the impact of the El Salvador regulation from a US point of view.

Hygiene requirements for cleaning and disinfection of surfaces: recommendation of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute.

This recommendation of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) addresses not only hospitals, but also outpatient health care facilities and compiles current evidence. The following criteria are the basis for the indications for cleaning and disinfection: Infectious bioburden and tenacity of potential pathogens on surfaces and their transmission routes, influence of disinfecting surface cleaning on the rate of nosocomial infections, interruption of cross infections due to multidrug-resistant organisms, and outbreak control by disinfecting cleaning within bundles. The criteria for the selection of disinfectants are determined by the requirements for effectiveness, the efficacy spectrum, the compatibility for humans and the environment, as well as the risk potential for the development of tolerance and resistance. Detailed instructions on the organization and implementation of cleaning and disinfection measures, including structural and equipment requirements, serve as the basis for their implementation. Since the agents for surface disinfection and disinfecting surface cleaning have been classified as biocides in Europe since 2013, the regulatory consequences are explained. As possible addition to surface disinfection, probiotic cleaning, is pointed out. In an informative appendix (only in German), the pathogen characteristics for their acquisition of surfaces, such as tenacity, infectious dose and biofilm formation, and the toxicological and ecotoxicological characteristics of microbicidal agents as the basis for their selection are explained, and methods for the evaluation of the resulting quality of cleaning or disinfecting surface cleaning are presented.

КІБЕРПРОМИСЛОВЕ ШПИГУНСТВО: СУТНІСТЬ ТА НАСЛІДКИ

The article highlights the theoretical aspects of cyber-industrial espionage. The importance of ensuring the protection of trade secrets of companies from cyber intrusions is substantiated, which is confirmed by the amount of damage caused by successful cyber attacks on the scale of the global economic space. The paper examines the essence of cyber industrial espionage through the prism of its comparison with cyber espionage and industrial espionage. It is established that cyber-industrial espionage is a type of cyber-espionage and industrial espionage. Its key features are illegality, unethicality, and unauthorised access by an unauthorised user to a company's trade secret in cyberspace, which is carried out in favour of private entities in order to gain competitive advantages and economic benefits. By the logic of the dialectical combination of the general and the particular, the author identifies the features inherent in cyber-industrial espionage (in particular, its covert, highly organised, planned, systematic nature; wide arsenal of possible technologies, methods of implementation, their combined use; a significant scope and list of negative consequences, difficulties in assessing losses from cyber intrusions, etc.), and reveals the peculiarities of their manifestation in cyberspace. Considerable attention is paid to identifying and clarifying the content of possible negative consequences of successful cyberattacks for companies, including financial losses associated with the theft of confidential information; reputational losses due to loss of trust in the company; theft of intellectual property, R&D results kept as commercial secrets; disruption of critical business processes of companies; forced changes in business practices to improve security, legal, regulatory, psychological and emotional consequences. Determination of the essential characteristics of cyber-industrial espionage and the range of possible negative consequences of its implementation is of theoretical and methodological importance for the development of an effective system of trade secret protection in companies and will help to increase the efficiency of its use.

Competitive changes and innovation practice: Analysis of R&D policy on the Brazilian electricity sector

The electricity sector is in the midst of structural changes accelerated by current trends such as digitalisation, decarbonisation, and decentralisation. This phenomenon led companies to explore new ways of innovating. However, some experts and practitioners argue that the current R&D regulation may limit strategic advancements. This paper aims to analyse the current R&D policy on the electricity sector in light of digital innovation efforts. The study focuses on the Brazilian regulatory framework for R&D activities, which has been evolving since the early 1990s. Therefore, the study presents a multiple case analysis of different projects aimed at innovation through digitalisation, highlighting the main bottlenecks and their relationships with the regulatory structure. The paper contributes by presenting a timeline of R&D regulatory changes within the Brazilian electricity sector, discussing the recent innovation movements, and detailing an organised structure on regulatory constraints and practical consequences, which could be useful when developing new policies and practices on innovation for energy sectors.

Agential cuts of regulatory science practices – the case of microplastics

Over the past decades, a new field of research related to microplastics has emerged which still faces a high degree of uncertainty and conflicting views regarding the risks posed by microplastics. To date, social research has not addressed the regulatory science practices necessary for assessing the risks created by microplastics and related ethical questions. Therefore, the objective of this article is to analyse the role of central regulatory science practices, that is, risk assessments as they relate to microplastics. I draw on the work of Karen Barad to conceptualise these regulatory science practices as boundary-drawing practices which produce agential cuts. I will show that scientific and regulatory boundary-drawing practices draw agential cuts determining the properties of microplastics and regulatory actions that have ‘real’ consequences for human and environmental health. My empirical case demonstrates that different versions of risk assessment exist – one based on thresholds and the other on persistence – each of which have different regulatory consequences. Threshold risk assessment does not legitimise action to regulate microplastics, because the threshold at which microplastics have toxic effects requires such high concentrations that industry could continue to emit microplastics for decades. Therefore, only risk assessments that relate to the materiality of microplastics in terms of persistence and accumulation legitimise regulatory action.

The post-breach threat landscape and the need for an ‘effective’ compliance programme

In today’s rapidly evolving cyber security landscape, organisations face a multitude of threats beyond traditional hackers and state actors. The aftermath of a data breach involves not only the immediate response and recovery efforts on the part of the breached organisation but also a complex web of regulatory and legal consequences. This paper delves into the often-overlooked challenges posed by regulatory enforcement and the potential collateral damage that organisations may face following a breach. By understanding these aspects, organisations can develop effective compliance programmes that mitigate risks and protect against legal repercussions.

Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.

Wilms tumors present as an amalgam of varying proportions of tissues located within the developing kidney, one being the nephrogenic blastema comprising multipotent nephron progenitor cells (NPCs). The recurring missense mutation Q177R in NPC transcription factors SIX1 and SIX2 is most correlated with tumors of blastemal histology and is significantly associated with relapse. Yet, the transcriptional regulatory consequences of SIX1/2-Q177R that might promote tumor progression and recurrence have not been investigated extensively. Utilizing multiple Wilms tumor transcriptomic datasets, we identified upregulation of the gene encoding non-canonical WNT ligand WNT5A in addition to other WNT pathway effectors in SIX1/2-Q177R mutant tumors. SIX1 ChIP-seq datasets from Wilms tumors revealed shared binding sites for SIX1/SIX1-Q177R within a promoter of WNT5A and at putative distal cis-regulatory elements (CREs). We demonstrate colocalization of SIX1 and WNT5A in Wilms tumor tissue and utilize in vitro assays that support SIX1 and SIX1-Q177R activation of expression from the WNT5A CREs, as well as enhanced binding affinity within the WNT5A promoter that may promote the differential expression of WNT5A and other WNT pathway effectors associated with SIX1-Q177R tumors.

OPTIMALISASI PERAN DAN FUNGSI LEMBAGA PENYELESAIAN DALAM SENGKETA PERTANAHAN DI KAWASAN PEDESAAN DALAM MEWUJUDKAN GOODWIL

The development of information and communication technology has had a significant impact on various sectors of life, including the banking sector. The legal system has made essential safeguards to protect bank and customer data security. The latest information regarding developments in the Indonesian Kapital data leak case must be sought through trusted news sources or contacting authorities such as the OJK or Bank Indonesia to obtain accurate and up-to-date information. The Consumer Protection Law seeks to protect bank customers by limiting standard clauses that cannot be avoided in today's banking business world. The method in this research uses normative legal research. Issues in the banking world relate to the legal position of banking in cases of leakage of Indonesian Sharia Bank customer data and banking legal protection efforts that the legal system has carried out to protect the security of bank data and customer data. Two factors cause leaks of customer personal data, namely internal and external factors. Cases of customer data leakage are severe violations of privacy and information security. Banks, including Islamic banks, have a big responsibility in maintaining the confidentiality of customer data and protecting their personal information. If a data leak occurs, the bank could face legal and regulatory consequences, potentially harming its reputation. The method in this research uses normative legal research.

ANALISIS UPAYA DAN PERAN PERLINDUNGAN HUKUM TERHADAP KASUS PERETASAN DATA BANK SYARIAH INDONESIA

The development of information and communication technology has had a significant impact on various sectors of life, including the banking sector. The legal system has made essential safeguards to protect bank and customer data security. The latest information regarding developments in the Indonesian Kapital data leak case must be sought through trusted news sources or contacting authorities such as the OJK or Bank Indonesia to obtain accurate and up-to-date information. The Consumer Protection Law seeks to protect bank customers by limiting standard clauses that cannot be avoided in today's banking business world. The method in this research uses normative legal research. Issues that occur in the banking world relate to the legal position of banking in cases of leakage of Indonesian Sharia Bank customer data and banking legal protection efforts that have been carried out by the legal system to protect the security of bank data and customer data. There are two factors that cause leaks of customer personal data, namely internal and external factors. Cases of customer data leakage are serious violations of privacy and information security. Banks, including Islamic banks, have a big responsibility in maintaining the confidentiality of customer data and protecting their personal information. If a data leak occurs, the bank could face legal and regulatory consequences, and could potentially harm their reputation. The method in this research uses normative legal research.

Quantification and stability assessment of 7,9-di‑tert‑butyl‑1-oxaspiro(4,5)deca-6,9-diene-2,8‑dione leaching from cross-linked polyethylene pipes using gas and liquid chromatography.

This study assesses the formation and stability of the water contaminant 7,9-di‑tert‑butyl‑1-oxaspiro(4,5)deca-6,9-diene-2,8‑dione ([1]) which repeatedly occurs in the migration waters of cross-linked polyethylene (PE-X) pipes. In aqueous solution [1] is partially transformed to 3-(3,5-di‑tert‑butyl‑1‑hydroxy-4-oxo-2,5-cyclohexadien-1-yl)propionic acid ([2]). For a better understanding of the formation of [1] and its transformation into [2] an analytical method was established to allow the analysis of both species separately. Because of thermal instability [2] cannot be detected with GC-MS. Therefore, two methods were validated for a reliable and reproducible quantification: GC-MS for [1] and HPLC-MS/MS for both [1] and [2]. Comparative measurements of migration waters from PE-X pipes using GC-MS and HPLC-MS/MS methods showed that the concentrations of [1] detected with GC-MS corresponds to the sum of [1] and [2] measured with HPLC-MS/MS. In the migration waters [1] was detected in higher concentrations than [2]. The highest concentrations of [1], detected with GC-MS, were > 300µg/L. The longer the materials are stored without contact with water, the more [1] is measured in the migration waters. Most of the previous values reported in the literature for [1] were based on semi-quantification. Hence, we compared results of the semi-quantitative determination according to EN 15768 with those of a quantitative method with a standard. The results gained with the semi-quantitative method represent less than 50% of the quantified values for the amount leaching from the pipes, which means that the semi-quantification method according to EN 15768 leads to a significant underestimation of [1]. Finally, stability assessment showed that [1] developed an equilibrium with [2] under acidic conditions, whereas it will completely be transferred to [2] at pH 10. At pH 7, it takes more than 50 days for [1] to reach an equilibrium with [2]. However, at increasing the temperature to 60°C, [1] will be rapidly transformed into [2]. Besides [1] and [2], other currently unknown degradation products are formed. As there is no comprehensive toxicological assessment for both substances available today, our findings underline the need for regulatory consequences.

Epigenetic Regulation of Subgenomic Gene Expression in Allotetraploid Brassica napus.

The allotetraploid Brasscia napus has now been extensively utilized to reveal the genetic processes involved in hybridization and polyploidization. Here, transcriptome, WGBS, and Chip-Seq sequencing data were obtained to explore the regulatory consequences of DNA methylation and histone modifications on gene expression in B. napus. When compared with diploid parents, the expression levels of 14,266 (about 32%) and 17,054 (about 30%) genes were altered in the An and Cn subgenomes, respectively, and a total of 4982 DEGs were identified in B. napus. Genes with high or no expression in diploid parents often shifted to medium or low expression in B. napus. The number of genes with elevated methylation levels in gene promoters and gene body regions has increased in An and Cn subgenomes. The peak number of H3K4me3 modification increased, while the peak number of H3K27ac and H3K27me3 decreased in An and Cn subgenomes, and more genes that maintained parental histone modifications were identified in Cn subgenome. The differential multiples of DEGs in B. napus were positively correlated with DNA methylation levels in promoters and the gene body, and the differential multiples of these DEGs were also affected by the degree of variation in DNA methylation levels. Further analysis revealed that about 99% of DEGs were of DNA methylation, and about 68% of DEGs were modified by at least two types of DNA methylation and H3K4me3, H3K27ac, and H3K27me3 histone modifications. These results demonstrate that DNA methylation is crucial for gene expression regulation, and different epigenetic modifications have an essential function in regulating the differential expression of genes in B. napus.