For risk communication, it is important to understand the difference between "hazard" and "risk". Definitions can be found in Codex Alimentarius and the European Union (EU) General Food Regulation (EC) No 178/2002. The use of these terms as synonyms or their interchange is a recurrent issue in the area of food safety, despite awareness-raising messages sent by EFSA (European Food Safety Authority) and other interested entities. A quick screening of EU’s food regulations revealed several inconsistencies. Hence, it was considered necessary to further investigate if regulations could act as a source for this problem. A software tool was developed to support the detection and listing of inconsistent translations of “hazard” and “risk” in certain EU food regulations. Subsequently, native-speaking experts working in food safety, from each EU country, were asked to provide their individual scientific opinion on the prepared list. All data was statistically analyzed after applying numerical scores (1-5) describing different levels of consistency. Results showed that the most common problem was the interchange of “hazard” with “risk” and vice versa. This lack of consistency can create confusion that can further translate into misjudgments at food risk assessment and communication level.

Glutamate dehydrogenase (GDH) plays a key role in the metabolism of glutamate, an important compound at a cross-road of carbon and nitrogen metabolism and a relevant neurotransmitter. Despite being one of the first discovered allosteric enzymes, GDH still poses challenges for structural characterization of its allosteric sites. Only the structures with ADP, and at low (3.5 Å) resolution, are available for mammalian GDH complexes with allosteric activators. Here we aim at deciphering structural basis for the GDH allosteric activation, using bovine GDH as a model. For the first time we report a mammalian GDH structure in a ternary complex with the activators leucine and ADP, co-crystallized with potassium ion. An improved 2.4 Å resolution of the GDH complex with ADP is also presented. The ternary complex with leucine and ADP differs from the binary complex with ADP by the conformation of GDH C-terminus, involved in the leucine binding and subunit interactions. The potassium site, identified in this work, may mediate interactions between the leucine and ADP binding sites. Our data provide novel insights into the mechanisms of GDH activation by leucine and ADP, linked to the enzyme regulation by (de)acetylation.

Connexins (Cxs) are transmembrane proteins that assemble into gap junction channels (GJCs) and hemichannels (HCs). Previous research supports the involvement of Rho GTPases and actin microfilaments in the trafficking of Cxs, formation of GJCs plaques, and regulation of channel activity. Nonetheless, it remains uncertain whether distinct types of Cxs HCs and GJCs respond differently to Rho GTPases or changes in actin polymerization/depolymerization dynamics. Our investigation revealed that inhibiting RhoA, a small GTPase that controls actin polymerization, or disrupting actin microfilaments with cytochalasin B (Cyto-B), resulted in reduced GJCs plaque size at appositional membranes and increased transport of HCs to non-appositional plasma membrane regions. Notably, these effects were consistent across different Cx types, since Cx26 and Cx43 exhibited similar responses despite having distinct trafficking routes to the plasma membrane. Functional assessments showed that RhoA inhibition and actin depolymerization decreased the activity of Cx43 GJCs while significantly increasing HCs activity. However, the functional status of GJCs and HCs composed of Cx26 remained unaffected. This study supports the hypothesis that RhoA, through its control of the actin cytoskeleton, facilitates the transport of HCs to appositional cell membranes for GJCs formation while simultaneously limiting the positioning of free HCs at non-appositional cell membranes, independently of Cx type. This dynamic regulation promotes intercellular communication and reduces non-selective plasma membrane permeability through a Cx-type dependent mechanism, whereby Cx43 HCs and GJCs are affected, but Cx26 channels are not.

Over the years, researchers have been studying the effect of weather and context data on the transport mode choice. The majority of these works are based on survey data, however the accuracy of their findings relies on how respondents give accurate and honest answers. In this paper, the potential of using GPS trajectories as an alternative to travel surveys in studying the impact of weather and context data on transport mode choices is investigated in Beijing city. In the analysis, we apply both descriptive and statistical models such as the MNL and MNP models. Our findings indicate that temperature has the most prominent effect among weather conditions. For instance, for temperatures greater than 25 °C, the walking share increases by 27% and the bike share reduces by 21%, which is line with the results from several survey studies. In addition, the evidence of government policy on transport regulation is revealed when the air quality becomes hazardous as people are encouraged to use environmentally friendly travel mode choices such as the bike instead of the bus and car, which are known CO2 emitters. Moreover, due to a series of traffic restrictions introduced by the Beijing government during the 2008 summer Olympics, a decrease of 17.5% in the car share and an increase of 13% and 10% in the walking and bus shares, respectively are observed. These findings provide a scientific basis for effective transport regulation and planning purposes.

In the process of expanding the application of electronic licenses in the Chinese agricultural sector, challenges such as inconsistent information standards, poor interoperability, significant data barriers, and lack of regulatory basis are encountered. By examining online information and practical data of agricultural electronic licenses in the 31 provincial-level administrative units in mainland China, variations in the reasons for promoting the expanded application of electronic licenses in different regions were identified. It is believed that strategies should be proposed around key factors such as government capacity, economic development, social needs, and intergovernmental relations. Suggestions include enhancing the intensity of information aggregation, diversifying the management entities, advancing the intelligence of underlying technology, and improving the completeness of legal rules. New conceptual proposals, such as constructing a database for agricultural information collection, establishing a multi-entity management authorization mechanism, implementing intelligent applications of electronic licenses at the grassroots level, and developing specialized legal rules, require further validation.

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

Increased construction activities in Australia have led to the generation of a massive volume of construction and demolition (C&D) waste annually. Management of this volume of waste requires an effective waste framework. The literature reported that the current Australian waste framework does not meet expectations and needs immediate improvements. This study was therefore conducted to seek the key C&D stakeholders' opinion about various issues identified in this waste stream. The specific objectives of this study are identification of the main barriers to effective C&D waste management, the impact of current regulations and opportunities to enhance the current C&D waste management system. A survey was conducted in 2019 to capture the stakeholders' perception. 132 participants from various industries and government agencies based in various Australian jurisdictions took part in the survey. The key results showed that the main barriers towards an effective management system are "overregulation, tough acceptance criteria, and increased testing requirements", "lack of local market" and "culture, poor education and low acceptance". Furthermore, a low number of participants indicated that the current legislation encourages waste recovery activities. The main areas of improvements included "providing a guideline that determines the accepted level of contamination for reusing C&D waste”, "preparation of guidelines on requirements of using recycled C&D materials in different industries" and "setting target for reduction, reusing, and recycling C&D waste". The results can inform policy development and be used as evidence for a broader discussion to solve lasting issues in C&D waste management.

Multi-modal Motion-assisted Memory Desensitization and Reprocessing Therapy (3MDR), an interactive, virtual-reality assisted, exposure-based intervention for PTSD, has shown promising results for treatment-resistant Posttraumatic Stress Disorder (TR-PTSD) among military members (MMs) and Veterans in Randomized Controlled Trials. Previous research has suggested that emotional regulation (ER) and emotional dysregulation (ED) may be factors which are correlated with symptom severity and maintenance of TR-PTSD. This embedded mixed-methods pilot study (n=9) sought to explore the impact of 3MDR on ER and ED of MMs and Veterans. Difficulties in Emotional Regulation Scale (DERS-18) data was collected at baseline, prior to each session, and at 1 week, 1 month and 3 months post-intervention and analyzed using a Wilcoxon signed-ranks test. Qualitative data collected from sessions, debriefs, and follow-up interviews were transcribed and descriptively analyzed. Results demonstrated statistically significant decreases in DERS-18 scores from pre-intervention to post-intervention at each timepoint. Qualitatively, participants perceived improvements in ER within specified DERS-18 domains. We describe how 3MDR’s unique and novel approach may address ED through cognitive-motor stimulation, narration, divergent thinking, reappraisal of aversive stimuli, dual-task processing, and reconsolidation of traumatic memories. Further investigation is underway to better understand the underlying neurobiological mechanisms by which 3MDR addresses ER and PTSD.

Non-coding RNAs, specifically microRNAs (miRNAs), exhibit altered expression and contribute significantly to the pathological processes observed in numerous diseases, encompassing various types of human cancers. Recent discoveries regarding miRNAs underscore their crucial roles in tumor pathogenesis and their responses to diverse therapeutic interventions. miRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in the miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive target genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many types of cancers functioning as either oncomiRs or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling deregulated miRNAs in many cancer types has been shown to correlate with disease diagnosis, indicate optimal treatment options, and predict response to a specific therapy. Specific miRNA signatures can track all stages of disease including many cancer types and hold potential as biomarkers and therapeutic targets as well as therapeutics as miRNA mimics and inhibitors (antagomirs). As such, identifying specific miRNAs and mRNAs they regulate in many types of cancer along with downstream pathways can be used as potential therapeutic targets. Because a single miRNA can regulate a pool of targets involved in similar cellular processes and pathways, thereby amplifying the cellular response, this potentially makes miRNAs powerful therapeutics to restore cell functions that are altered as part of a disease phenotype. However, because a single miRNA regulates multiple gene expressions their cellular effects are numerous leading to potential off-target effects. Besides their intended targeting issues, there is a need to reduce the immunogenic reactions and determine the minimal dosing to achieve the desired effect while minimizing side effects. As such, a careful risk evaluation of miRNA therapeutics is needed to minimize off-target effects and to avoid overdosing of miRNA drugs. Furthermore, a limited understanding and validation of the specific roles of miRNAs limits their clinical application. In addition, there are many challenges concerning the delivery, sensitivity, specificity, toxicity, and applicability of the potential utility of miRNAs as therapeutic targets or therapeutics. Thus, future work will warrant if miRNAs can be used as cancer biomarkers as well as therapeutics for clinical application.

Drinking water, in addition to the best-known chemical and biological agents, contains radionuclides of both natural and artificial origin, which can contribute significantly to the overall effective dose received by the population. The Italian Decree Law 28/2016, implementing 2013/51/EURATOM Directive, establishes the activities for risk management and the parameter values for different radionuclides activity concentrations. In addition to the institutions involved, annually the National Inspectorate for Nuclear Safety and Radiation Protection (ISIN), publishes the monitoring reports of environmental radioactivity in Italy, including radioactivity in drinking water. The purpose of the study was to integrate ISIN reports with 2018 to 2020 data by collecting measurements performed by institutional laboratories to obtain a more complete information and adding, for the Campania region, some data not yet published. This new updated report was not significantly different from ISIN’s one, meaning that those publications are nevertheless extremely representative of the radioactivity in Italian drinking water. However, the study allowed to obtain a more detailed data also including measurements not considered in ISIN reports, for instance, radon-222 activity concentrations. This may be of great usefulness for all radiation protection stakeholders in order to ensure environmental protection, pollution prevention and the population safety.

Ferric uptake regulation protein is a repressor protein which binds an AT rich region of DNA (the iron box). Fur binds as a dimer in a helix turn helix mode and it is activated by iron(II) and other divalent transition metal ions at elevated concentrations in a process to regulate the ion uptake. Each transition metal ion induces certain conformational changes to aid the Fur binding, both the N-terminal and C-terminal domains take part in binding to DNA in addition to His 88 and His 86 residues. The process is discussed in view of experimental reports. Fe(II), Mn(II) and Co(II) activate Fur to bind DNA experimentally but Zinc plays a structural role and does not activate Fur to bind DNA.

This mini-review provides an overview of traditional, emerging, and future applications of lactic acid bacteria (LAB) and discusses how genome editing tools can be used to overcome current challenges in all these applications. It also describes currently available tools and how these can be further developed, and takes current legislation into account. Genome editing tools are necessary for the construction of strains for new applications and products, but can also play a crucial role in traditional ones, such as food and probiotics, as a research tool for understanding mechanistic insights and discovering new properties. Traditionally, recombinant DNA techniques for LAB have strongly focused on being food-grade, but they lack throughput and the number of genetically tractable strains is still rather limited. Further tool development in this direction will enable rapid construction of multiple mutants or mutant libraries on a genomic level in a wide variety of LAB strains. We also propose an iterative Design-Build-Test-Learn workflow cycle for LAB cell factory development based on systems biology, with “cell factory” expanding beyond its traditional meaning of production strains and making use of high-throughput genome editing tools to advance LAB understanding, applications and strain development.

Intramuscular fat content (IFC) and meat color are vital indicators affecting pork quality. A significant positive correlation between IFC and redness meat color (a* value) indicates that these two traits are likely to be regulated by shared molecular pathways. To identify candidate genes, hub genes, and signaling pathways that regulate these two traits, we measured the IFC and a* value in 147 hybrid pigs and selected individuls with extreme phenotypes for transcriptome analysis. The results revealed 485 and 394 overlapping differentially expressed genes (DEGs) using DESeq2, limma, and edgeR packages affecting IFC and a* value, respectively. Weighted gene co-expression network analysis (WGCNA) identified four modules significantly correlated with IFC and a* value. Moreover, we integrated functional enrichment analysis results based on DEGs, GSEA, and WGCNA conditions to identify candidate genes, and identified 47 and 53 candidate genes affecting IFC and a* value, respectively. The protein-protein interaction (PPI) network analysis of candidate genes showed that 6 and 14 hub genes affecting IFC and a* value, respectively. These genes mainly participated in various pathways related to lipid metabolism and redox reactions. Notably, four crucial hub genes (MYC, SOX9, CEBPB, and PPAGRC1A) were shared for these two traits. After functional annotation of these four hub genes, we hypothesized that the SOX9/CEBPB/PPARGC1A axis could co-regulate lipid metabolism and myoglobin redox response. Further research on these hub genes, especially the SOX9/CEBPB/PPARGC1A axis, will help to understand the molecular mechanism of the co-regulation of IFC and a* value, which will provide the theoretical basis for improving pork quality.

The Forest Stewardship Council initiated a pilot Forest Certification for Ecosystem Services (ForCES) project from 2011 to 2017 to improve and promote sustainable forest management addressing a range of ecosystem services. Three sites in Indonesia were studied in the pilot. Whilst the development of the certification standard was largely by a partnership between the certification standard organization, civil society and research organisations, implementation and monitoring of the impact of this voluntary sustainability standard will entail interaction with state regulations. This study sought to understand how certification and state regulations concerning ecosystem services in Indonesia interplay, particularly in the agenda setting and negotiation stage. Using the conceptual lenses of transition theory and state and non-state market-based governance, the interrelationships between ecosystem services certification and regulations were found to be both complementary, supporting and antagonistic. The majority were complementary. Antagonism occurred where regulations do not accommodate land use issues and due to different contradictory state regulations. The voluntary instruments were developed largely in the absence of state involvement and without any substitution with regulatory standards. Given the increasing proliferation of voluntary market-driven initiatives at farm, forest concession and landscape level, stakeholders developing and managing voluntary standards need to collaborate with national and local governments to create synergy to enable their acceptance, adoption and effectiveness to positively enhance the conservation of ecosystem services through incentivizing market-based instruments.

Fatty acids play a major role in determining membrane biophysical properties. Staphylococcus aureus produces branched-chain fatty acids (BCFAs) and straight-chain fatty acids (SCFAs), and can incorporate exogenous SCFAs and straight-chain unsaturated fatty acids (SCUFAs). Many S. aureus strains produce the triterpenoid pigment staphyloxanthin, and the balance of BCFAs, SCFAs and staphyloxanthin determines membrane fluidity. Here, we investigated the relationship of fatty acid and carotenoid production in S. aureus using a pigmented strain (Pig1), its carotenoid-deficient mutant (Pig1ΔcrtM) and the naturally non-pigmented Staphylococcus argenteus that lacks carotenoid biosynthesis genes and is closely related to S. aureus. Fatty acid compositions in all strains were similar under a given condition indicating that staphyloxanthin does not influence fatty acid composition. Strain Pig1 had decreased membrane fluidity as measured by fluorescence anisotropy than the other strains under all conditions indicating that staphyloxanthin helps maintain membrane rigidity. We could find no evidence for correlation of expression of crtM and fatty acid biosynthesis genes. Supplementation of medium with glucose increased SCFA production and decreased BCFA and staphyloxanthin production, whereas acetate-supplementation also decreased BCFAs but increased staphyloxanthin production. We believe that staphyloxanthin levels are influenced more through metabolic regulation than responding to fatty acids incorporated into the membrane.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth and proliferation by down-regulating PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury and immune response. Therefore, recently PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Here we provide an overview of studies that highlight the role of oxidative inhibition of PTEN in physiological processes.

In their natural environment, bacteria are exposed to various stresses. The stress-response sigma factor SigB of gram-positive Bacillus subtilis is the best-characterized example. Unlike Bacillus subtilis, the gram-positive bacterium Streptomyces coelicolor A3(2) contains nine SigB homologues (SigBFGHIKLMN) with a major role in differentiation and response to osmotic stress. We previously constructed a two-plasmid system to identify promoters recognized by these sigma factors. Interestingly, almost all identified promoters were recognized by two or more SigB homologues. However, no specific sequences characteristic for these recognition groups were found. To examine this cross-recognition in vivo in S. coelicolor A3 (2), one of these promoters was cho-sen, which drives the expression of the sporulation-specific gene ssgB. The ssgBp promoter was inserted into a luciferase reporter plasmid and conjugated to S. coelicolor M145 and nine mutant strains containing deleted individual sigB homologous genes. Luciferase reporter activity indi-cated differential activity of this promoter in these mutant strains, suggesting overlapping pro-moter recognition by these SigB homologues. To determine which nucleotides in the ̶ 10 re-gion are responsible for the selection of a specific SigB homologue, several mutant promoters with altered last three nucleotides in this region were prepared and tested in the two-plasmid system. Some mutant promoters were specifically recognized by some SigB homologues. Mutant promoters were inserted into a luciferase reporter plasmid and conjugated to S. coelicolor A3(2) and these nine mutant strains. Luciferase reporter activity indicated differential activity of these ssgBp mutant promoters, indicating overlapping promoter recognition by these SigB homologues in S. coelicolor A3(2).

Assistance dogs provide significant benefits to older adult owners. However, despite protective legislation, aged care facilities continue to not allow owners to retain their dog on relocation. The purpose of the current study was to explore whether older adults should be allowed to retain their dog on relocation to an aged care facility, and what factors should impact this decision. Further, if allowed to retain their dog, what would be the best practice to allow for this. A deliberative democracy methodology was used, with a range of key stakeholders recruited. Focus groups were held, with follow up questionnaire to establish deliberation for all questions. Results indicated that with sufficient objective measurement, fair decisions can be made to ensure the welfare and wellbeing for owner and dog. Key policy and procedure changes would also be necessary to ensure ongoing support, such as training, care plans, and emergency directives. By ensuring sufficient policies and procedures are in place, training and support could lead to an ideal outcome where facilities could be at the forefront of a better future for aged care.

KLFs seem to associate with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of differentiation of cardiac myofibroblasts or a modified fatty acid oxidation, related to the formation of a dilated cardiomyopathy; myocardial infarctions, left ventricular hypertrophy and diabetic cardiomyopathies. MicroRNA have been involved in certain regulatory loops of KLFs as they may function as critical modulators of vascular smooth muscle cells in atherosclerosis, in heart failure and as markers of endothelial damage in acute myocardial infarction.

The stringency of GMO regulation affects trade of agricultural products among countries. On that account, our investigation attempts to shed the light on the complexity of the impact of genetically modified organisms (GMO) regulations among countries on bilateral trade with a focus on GMO approvals. We develop a framework extending Xiong and Beghin (2014) and their decomposition of export supply and imports demand effects. Our approach encompasses the supplemental effect of GMO regulation laxity in production on the exporter’s productivity. It decomposes three effects that impact bilateral trade flows between trade partners: productivity in the source country, sorting cost from bilateral dissimilarity in regulations, and stringency impact on import demand. We estimate the model using a panel dataset of corn trade and two econometric approaches (PPML, Heckman sample-selection). We find that GMO laxity in production of exporters has the most prominent and robust effect of enhancing bilateral trade of corn. The effect of GMO laxity in demand appears to be smaller than the export booster effect of GMO adoption. Finally, bilateral dissimilarity in regulations does not appear to matter, once we account for the impact of GMO in production of the exporters and laxity in demand differentiated for importer and exporters. Hence, GMO approval regulations have dominating multilateral effects rather than bilateral ones.

Introduction: The application of the concept of self-regulation that has an impact on the psychological well-being of adolescent social media users as self-regulation in a core aspect of human functioning that helps facilitate the successful pursuit of personal goals and adaptability to changes in the environment. This literature aims to determine the study of the psychological well-being philosophy of adolescent social media users based on self-regulation.Methods: This literature study was conducted through a search for scientific publications ranging from 2018-2022. The databases used are PubMed, Science Direct, and ProQuest. The literature search was carried out according to topics with four groups of keywords based on Medical Subject Heading (MeSH) and combined with Boolean operators AND, OR and NOT, keywords Self-regulation AND mental wellbeing AND social media AND adolescence.Results: A study of the psychological well-being of adolescent social media users based on self-regulation based on ontology, epistemology, and axiology studies. Self-regulation is a philosophy that emphasizes the dynamic process that directs the behavior of a teenager towards the desired final state and adapts to changes that occur in the surrounding environment. The adaptation process is carried out as a form of self-regulation of the positive and negative impacts of using social media on adolescents with a motivational approach and avoidance system. The approach motivation system is carried out if it provides positive aspects in social media. While avoidance motivation is carried out if it has a negative impact in the form of low self-esteem, depression, and body image disturbances as a result of social comparisons made by teenagers when they see other people's posts.Conclusion: The concept of psychological well-being of adolescent social media users based on self-regulation is beneficial for parents to improve the parenting pattern of adolescent children. Good parenting is needed in understanding the positive and negative impacts of using social media and reducing externalization problems in adolescents.

JmjC-family of lysine demethylases (JMJC-KDMs) plays an essential role controlling gene expression and chromatin structure. In most cases, their function has been attributed to the demethylase activity. However, accumulating evidence demonstrates that these proteins play roles distinct from histone demethylation. This raises the possibility that they might share domains that contribute to their functional outcome. Here, we show that the JMJC-KDMs contain low complexity domains as well as intrinsically disordered regions, which in some cases reached 70% of the protein. Our data revealed that PHF2, KDM2A and KDM4B cluster by phase-separation in vitro and in vivo. Moreover, our molecular analysis demonstrated that these domains are important to regulate transcription, suggesting that clustering via phase -separation is a common feature that JMJC-KDMs utilize, in addition to their catalytic activity, to facilitate their functional responses. Our study uncovers a novel potential function for the JMJC-KDM family that sheds light on the mechanisms to achieve the competent concentration of molecules in time and space within the cell nucleus.

Crocodilepox virus (CRV) belongs to the Poxviridae family and mainly infects hatchling and juvenile Nile crocodiles. Most poxviruses encode inhibitors of the host antiviral protein kinase R (PKR), which is activated by viral double-stranded (ds) RNA formed during virus replication, resulting in the phosphorylation of eIF2 and subsequent shutdown of general mRNA translation. Because CRV lacks orthologs of known poxviral PKR inhibitors, we experimentally characterized one candidate (CRV157), which contains a predicted dsRNA-binding domain. Bioinformatic analyses indicated that CRV157 evolved independently from other poxvirus PKR inhibitors. CRV157 bound to dsRNA, co-localized with PKR in the cytosol, and inhibited PKR from various species. To analyze whether CRV157 could inhibit PKR in the context of a poxvirus infection, we constructed recombinant vaccinia virus strains that contain either CRV157 or a mutant CRV157 deficient in dsRNA binding in a strain that lacks PKR inhibitors. The presence of wild type CRV157 rescued vaccinia virus replication, while the CRV157 mutant did not. The ability of CRV157 to inhibit PKR correlated with virus replication and eIF2alpha phosphorylation. The independent evolution of CRV157 demonstrates that poxvirus PKR inhibitors evolved from a diverse set of ancestral genes in an example of convergent evolution.

Obesity is a problem in the last decades since the development of different technologies forced the submission of a faster pace of life, resulting in nutrition style changes. In turn, domestic pigs are an excellent animal model in recognition of adiposity-related processes, corresponding to the size of individual organs, the distribution of body fat in the organism, and similar metabolism. The present study applied the next-generation sequencing method to identify adipose tissue (AT) transcriptomic signals related to increased fat content by identifying differentially expressed genes (DEGs), included long-non coding RNA molecules. The Freiburg RNA tool was applied to recognise predicting hybridisation energy of RNA-RNA interactions. The results indicated several long non-coding RNAs (lncRNAs) whose expression was significantly positively or negatively associated with fat deposition. lncRNAs play an essential role in regulating gene expression by sponging miRNA, binding transcripts, facilitating translation, or coding other smaller RNA regulatory elements. In the pig fat tissue of obese group, increased expression of lncRNAs corresponding to human MALAT1 was observed that previously recognised in the obesity-related context. Moreover, hybridisation energy analyses pinpointed numerous potential interactions between identified differentially expressed lncRNAs, and obesity-related genes and miRNAs expressed in AT.

Transposable elements (TEs), also known as mobile elements (MEs), are interspersed repeats that constitute a major fraction of the genomes of higher organisms. As one of their important functional impacts on gene function and genome evolution, TEs participate in regulating the expression of genes nearby and even far away at transcriptional and post-transcriptional levels. There are two known principal ways by which TEs regulate expression of genes. First, TEs provide cis-regulatory sequences in the genome with their intrinsic regulatory properties for their own expression making them potential factors for regulating the expression of the host genes. TE-derived cis-regulatory sites are found in promoter and enhancer elements, providing binding sites for a wide range of trans-acting factors. Second, TEs encode for regulatory RNAs with their sequences showed to be present in a substantial fraction of miRNAs and long non-coding RNAs (lncRNAs), indicating the TE origin of these RNAs. Furthermore, TEs sequences were found to be critical for regulatory functions of these RNAs including binding to the target mRNA. TEs thus provide crucial regulatory roles by being part of cis-regulatory and regulatory RNA sequences. Moreover, both TE-derived cis-regulatory sequences and TE-derived regulatory RNAs, have been implicated to provide evolutionary novelty to gene regulation. These TE-derived regulatory mechanisms also tend to function in tissue-specific fashion. In this review, we aim to comprehensively cover the studies regarding these two aspects of TE-mediated gene regulation, mainly focusing on the mechanisms, contribution of different types of TEs, differential roles among tissue types, and lineage specificity, based on data mostly in humans.

On 25 May 2018, the General Data Protection Regulation (GDPR)Article 17, the Right to Erasure (‘Right to be Forgotten’) came into force making it vital for organisations to identify, locate and delete all Personally Identifiable Information (PII) where a valid request is received from a data subject to erase their PII and the contractual period has expired. This must be done without undue delay and the organisation must be able to demonstrate reasonable measures were taken. Failure to comply may incur significant fines, not to mention impact to reputation. Many organisations do not understand their data, and the complexity of a hybrid cloud infrastructure means they do not have the resources to undertake this task. The variety of available tools are quite often unsuitable as they involve restructuring so there is one centralised data repository. This research aims to demonstrate compliance with GDPR’s Article 17 Right to Erasure (‘Right to be Forgotten’) is achievable in a Hybrid cloud environment by following a list of recommendations. However, 100% retrieval, 100% of time will not be possible, but we show that small organisations running an ad-hoc Hybrid cloud environment can demonstrate that reasonable measures were taken to be Right to Erasure (‘Right to be Forgotten’) compliant.

The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded and transfected in vitro with short hairpin Lentivirus targeting NANOG. Gene suppressions were achieved at both transcript and proteome levels. The effect of NANOG knockdown on proliferation after 10 passages and on the cell cycle was evaluated by proliferation assay, colony forming unit (CFU), qRT-PCR and cell cycle analysis by flow-cytometry. Moreover, NANOG involvement in differentiation ability was evaluated. We report that downregulation of NANOG revealed a decrease in the proliferation and differentiation rate, inducing cell cycle arrest by increasing p27/CDKN1B (Cyclin-dependent kinase inhibitor 1B) and p21/CDKN1A(Cyclin-dependent kinase inhibitor 1A) through p53 and regulate DLK1/PREF1. Furthermore, NANOG induced downregulation of DNMT1, a major DNA methyltransferase responsible for maintaining methylation status during DNA replication probably involved in cell cycle regulation. Our study confirms that NANOG regulates the complex transcription network of plasticity of the cells, inducing cell cycle arrest and reducing differentiation potential.

Indonesian crypto asset owners are expanding despite the government's ban. Crypto assets are too risky for Indonesian investors. This study uses the Theory of Planned Behavior and exogenous variables like financial literacy, trust, and government regulation to determine the causes of the intention to invest in crypto assets. Exogenous variables and behavioral intentions were moderated by gender. The study employs a quantitative approach, collecting data through a questionnaire survey of 149 adults over the age of 17 who have invested in non-crypto assets. SmartPLS was used to analyze research data. Financial literacy and trust, according to the study's findings, have an impact on the intention to invest in crypto assets. Gender can moderate the relationship between belief and behavioral intention. Women are more likely than men to invest in crypto assets due to the block chain system's security, transparency, and ease of use. This research is expected to help the government address the risks associated with investing in crypto assets by increasing transaction security with futures clearing and monitoring by using third parties as depositors. It also governs the laws governing crypto exchanges' liability to their investors.

RNA-guided genomic transcriptional regulation tools, namely Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) and CRISPR-mediated gene activation (CRISPRa), are a powerful technology for the field of functional genomics. Deriving from the CRISPR/Cas9 system, both systems comprise a catalytically dead Cas9 (dCas9) and a single guide RNA (sgRNA). This type of dCas9 is incapable of cleaving DNA but retains its ability to specifically bind to DNA. The binding of the dCas9/sgRNA complex to a target gene results in transcriptional interference. The CRISPR/dCas9 system has been explored as a tool for transcriptional modulation and genome imaging. Despite its potential applications and benefits, the challenges and limitations faced by the CRISPR/dCas9 system include the off-target effects, PAM sequence requirement, efficient delivery methods, and the CRISPR/dCas9-interfered crops being labeled as genetically modified organisms in several countries. This review highlights the progression of CRISPR/dCas9 technology as well as its applications and potential challenges in crop improvement.

In this manuscript we use an exactly solvable stochastic binary model for regulation of gene expression to analyse the dynamics of response to a treatment aiming to modulate the number of transcripts of RKIP gene. We demonstrate the usefulness of our method simulating three treatment scenarios aiming to reestablish RKIP gene expression dynamics towards pre-cancerous state: i. to increase the promoter’s ON state duration; ii. to increase the mRNAs’ synthesis rate; iii. to increase both rates. We show that the pre-treatment kinetic rates of ON and OFF promoter switching speeds and mRNA synthesis and degradation will affect the heterogeneity and time for treatment response. Hence, we present a strategy for reducing drug dosage by simultaneously targeting multiple kinetic rates. That enables a reduction of treatment response time and heterogeneity which in principle diminishes the chances of emergence of resistance to treatment. This approach may be useful for inferring kinetic constants related to expression of antimetastatic genes or oncogenes and on the design of multi-drug therapeutic strategies targeting master regulatory genes.

The move to a low carbon economy is very important for enhancing international competitiveness. The eco-innovation is the critical factor of the green paradigm. This study is designed to investigate deeply the determinants of eco-innovation of manufacturing firms in Korea by suggesting anticipated regulations, self-regulations, and industry-specific characteristics as external factors and open information sources as internal factors. The data used in the analysis is 1946 sample firms from Korean Innovation Survey 2010 based on the Oslo Manual. Using the multi-variate probit analysis and the zero-inflated negative binomial (ZINB) regression analysis, we have found out that the anticipated regulations and self-regulations have significant influences both on eco-process innovation and eco-product innovation, while industrial characteristics have no effects. The empirical results also show that the breadth of information sources has a positive effect on businesses in implementing eco-innovations. Our findings show that the Korean government should provide a good platform where firms can better understand the future trends of environmental policies, particularly policies on anticipated and self-regulations. At the same time, Korean firms should establish a voluntary system to control environmental activities so that they can improve eco-innovations through integrating external information.

Advancements in genomics and molecular biology have propelled our understanding of genetic information far beyond the iconic double helix structure of DNA. This comprehensive review delves into the intricate world of DNA and RNA networks, exploring the complexities that extend beyond the classical model. We investigate the dynamic interactions, regulatory mechanisms, and functional implications of the broader genetic landscape, encompassing both coding and non-coding elements. From chromatin architecture to the diverse array of non-coding RNAs, this exploration seeks to provide a holistic perspective on the multifaceted roles played by DNA and RNA in cellular processes. The three-dimensional organization of genetic material within the cell has emerged as a crucial determinant of cellular function. Chromatin architecture, comprising DNA, histones, and other associated proteins, plays a dynamic role in regulating gene expression. We delve into the intricate choreography of chromatin remodeling, deciphering the interplay between transcription factors, epigenetic modifications, and higher-order structures that modulate gene activity. The exploration of chromatin dynamics unveils a nuanced understanding of how the genome responds to environmental cues, cellular signals, and developmental processes. Moreover, the once-dismissed non-coding portion of the genome has emerged as a key regulator of cellular function. Various classes of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been implicated in diverse cellular processes, ranging from fine-tuning gene expression to modulating chromatin structure. The review critically examines the functional roles of these non-coding RNAs, shedding light on their involvement in cellular homeostasis, development, and disease. As I traverse this landscape beyond the double helix, our review synthesizes current knowledge on the intricacies of DNA and RNA networks. By exploring the regulatory mechanisms, functional implications, and emerging paradigms, we aim to inspire a deeper appreciation for the molecular choreography that underlies the cellular symphony of life. Furthermore, we discuss the implications of these findings in the context of disease, highlighting potential diagnostic and therapeutic avenues that arise from a comprehensive understanding of DNA and RNA networks. In doing so, this exploration not only broadens our theoretical understanding but also opens new frontiers for translational research in genetics and molecular medicine.

Mature B cells notably diversify immunoglobulin (Ig) production through class switch recombination (CSR), allowing the junction of distant “switch” (S) regions. CSR is initiated by activation-induced deaminase (AID) which targets cytosines adequately exposed within single-stranded DNA of transcribed targeted S regions, with a specific affinity for WRCY motifs. In mammals, G-rich sequences are additionally present in S regions, forming canonical G-quadruplexes (G4s) DNA structures which favor CSR. Small molecules interacting with G4-DNA (G4 ligands), proved able to regulate CSR in B lymphocytes, either positively (such as for nucleoside diphosphate kinase isoforms) or negatively (such as for RHPS4). G4-DNA is also implicated in the control of transcription, and due to their impact on both CSR and transcriptional regulation, G4-rich sequences likely play a role in the natural history of B cell malignancies. Since G4-DNA stands at multiple locations in the genome, and notably within oncogene promoters, it remains to be clarified how it can more specifically promote legitimate CSR in physiology, rather than pathogenic translocation. The specific regulatory role of G4 structures in transcribed DNA and/or in corresponding transcripts and recombination hereby appears as a major issue for understanding immune responses and lymphomagenesis.

Iris laevigata Fisch. is a perennial aquatic plant with strong cold resistance and showy flowers. However, the flowering period of a single flower is only two days, greatly limiting its potential use in landscaping and the cutting-flower industry. In addition, I. laevigata is often challenged with various abiotic stresses including high salinity and drought in its native habitat. Thus, breeding novel cultivars with prolonged flowering time and higher resistance to abiotic stress is of high importance. In this study, we first performed genome-wide identification of WRKYs, key transcription factors in modulating flowering time and abiotic stress responses. We overexpressed IlWRKY22 in Arabidopsis thaliana and found the flowering time was delayed in the transgenic plants. Molecular characterization further revealed that IlWRKY22 promotes the expression of CO and GA20OX genes in the photoperiod and gibberellin pathways, respectively, and inhibits the expression of SPL3 in the aging pathway. We also created transgenic Nicotiana tabacum overexpressing IlWRKY22, which showed significantly improved resistance to both salt and drought compared to control plants. Specifically, the photosynthetic rate, maximum potential quantum efficiency of Photosystem II (Fv/Fm), and chlorophyll content were higher in the transgenic plants, which was accompanied with higher antioxidant enzyme activity and lower levels of reactive oxygen species. Thus, our study revealed a unique dual function of IlWRKY22, an excellent candidate gene for breeding novel I. laevigata cultivars of desirable traits.

Apoptosis, the programmed and intentional death of senescent, damaged, or otherwise superfluous cells, is the natural end-point for most cells within multicellular organisms. Apoptotic cells are not inherently damaging, but if left unattended they can lyse through secondary necrosis. The resulting release of intracellular contents drives inflammation in the surrounding tissue and can lead to autoimmunity. These negative consequences of secondary necrosis are avoided by efferocytosis—the phagocytic clearance of apoptotic cells. Efferocytosis is a product of both apoptotic cell and efferocyte mechanisms, which cooperate to ensure the rapid and complete removal of apoptotic cells. Herein, the processes used by apoptotic cells to ensure their timely removal, and the receptors, signaling, and cellular processes used by efferocytes to identify, remove, and process the apoptotic cells, are reviewed.

: Efficient or at least rational use of energy resources is a problem that occupies an overwhelming number of people in modern society – from major scientists and politicians to journalists and schoolchildren who have a poor understanding of the basic laws of physics.(the knowledge of politicians in this area is also sometimes doubtful). At the same time, the main focus of the discussions is on the resource base, possible waste and consequences. According to these features, they want to see the future of energy. However, the division of "energetik" follows different principles. On the one hand, these are thermal, nuclear and hydropower sources. On the other – wind and solar energy. Obviously, this separation is not only related to the renewable resources or the absence of consequences for the environment and humans. If we do not touch on geopolitical problems. which are not the subject of this article, it is obvious that the main dividing feature of these types of energy production will be their controllability. The theory of automatic control (TAU) is one of the most complex modern sciences that has been developing for many years to solve precisely the problems of energy Now, when considering energy problems, this science is most often not remembered. Maybe because the most active participants in the discussions don't know much about it? Or is this situation beneficial to someone? How efficiency and controllability are related to some problems with controllability in the "household" energy sector, which concerns almost every inhabitant of the planet and in the global energy sector, this article is devoted to

The advent of CRISPR/Cas9 technology has revolutionized genome editing, enabling the attainment of once-unimaginable goals. CRISPR/Cas's groundbreaking attributes lie in its simplicity, versatility, universality, and its independence from customized DNA-protein systems, erasing the need for specialized expertise and broadening its scope of applications. Beyond its editing prowess, the discovery of novel Cas-based systems has spawned an array of additional biotechnological tools, empowering both fundamental and applied research. Researchers have harnessed CRISPR/Cas for gene regulation, deepening insights into gene expression and epigenetic changes. Precisely targeting DNA or RNA sequences, CRISPR/Cas effectively identifies and counters pathogens. Furthermore, it aids in genome imaging and sequencing, revealing genome spatial organization and chromatin dynamics. The non-editing applications of CRISPR/Cas exhibit tremendous potential across diverse domains, including diagnostics, biotechnology, and fundamental research. This article reviews and critically evaluates the primary CRISPR/Cas-based tools developed for plants and animals, underlining their transformative impact.

Mycotoxins are deleterious fungal secondary metabolites that contaminate food and feed, thereby creating concerns regarding food safety. Common fungal genera can easily proliferate in Indian tropical and sub-tropical conditions, and scientific attention is warranted to curb its growth. To address this, two nodal governmental agencies, namely the Agricultural and Processed Food Products Export Development Authority (APEDA) and Food Safety and Standards Authority of India (FSSAI), have developed and implemented analytical methods and quality control procedures to monitor mycotoxin levels in a range of food matrices and assess risks to human health over the past two decades. However, comprehensive information on such advancements in mycotoxin testing and issues in implementing these regulations is inadequately covered in recent literature. The aim of this review is thus to uphold a systematic picture of the role played by the FSSAI and APEDA for mycotoxin control at the domestic level and for the promotion of international trade along with certain challenges in dealing with mycotoxin monitoring. Additionally, it unfolds various regulatory concerns regarding mycotoxin mitigation in India. Overall, it provides valuable insights to the Indian farming community, food supply chain stakeholders, and researchers about India’s success story in arresting mycotoxins throughout the food supply chain.

The Attentional Control Theory (ACT) suggests that trait anxiety does not directly affect performance but may alter processing efficiency through the generation of compensatory strategies. However, the ACT does not describe the nature of these strategies, which could be reflective in nature. One hundred ten students (M = 20.12; SD = 2.10) completed questionnaires on trait anxiety, metacognitive beliefs, and emotion regulation strategies (ERS). They performed two working memory tasks: the digit span task from the WAIS-IV and an emotional n-back task. Anxiety, metacognitive beliefs, and maladaptive ERS were not linked to performance but were associated with longer response times. Additionally, participants using maladaptive ERS, such catastrophizing and rumination, made fewer negative commission errors and employed more strategies during the digit span. These findings support the role of the reflective level in influencing trait anxiety's impact on performance and emphasize considering metacognitive beliefs and maladaptive ERS for a comprehensive understanding of the ACT. Identifying these variables provides insights to optimize cognitive abilities and promote academic success.

Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive “cheat codes” for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated “do” and “don’t” guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans.

The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite’s strong dependence on this pathway and significant structural differences of its glycolytic enzymes compared to their human counterpart, glycolysis is considered as a potential drug target. In this study, we provide the first three-dimensional protein structure of P. falciparum hexokinase (PfHK), containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion which lines the active site. Moreover, we propose that this insertion plays a role upon ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both Sglutathionylation and Snitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.

The Pandemic in 2019 forced a digital adaptation with direct consequences on all educational stakeholders. On behalf of teachers and trainers, while many regarded these changes with some scepticism, others embraced the opportunity to integrate technology into their teaching methods and as learning resources. As translation trainers, it is essential to follow and understand the translation market. Thus, the exponential changes that digital technology has brought to this sector over the years impose constant shifts in teaching and learning methods and resources. In fact, translators require vast competencies, amongst which is the flexibility to adapt. In translation training Project-Based Learning (PBL) has been established as an essential teaching and learning method, as it has proven to foster the development of competencies as it simulates the translator's work environment. Thus, the need to adapt new strategies reinforced PBL and its benefits. PBL, however, similar to a freelance translator, places the student in the centre of the learning process, where self-regulation becomes essential, as it is necessary to analyse the market/situation and be flexible enough to adapt to the context accordingly. As of 2018-2019, technical translation courses at ISCAP have implemented PBL as their main teaching and learning method. At the same time, a study on student self-regulation began. The purpose was to understand student perception on their own self-regulation competence and its development or lack thereof after one year of PBL. Results indicate that PBL is seen as a useful simulation of the translation labour market and that it does enhance many essential competences, amongst which is student self-regulation.

According to known laws of physics, chronic positive mass balance is the actual etiology of obesity, not positive energy balance. The relevant physical law in terms of body mass regulation is the Law of Conservation of Mass, not the Law of Conservation of Energy. A recently proposed mass balance model (MBM) describes the temporal evolution of body weight and body composition under a wide variety of feeding experiments, and it seems to provide a highly accurate description of the very best experimental human feeding data. By shifting to a mass balance paradigm of obesity, a deeper understanding of this disease may follow in the near future. The purpose of this living review is to present the core issues of the upcoming paradigm shift as well as some practical applications related to the topic.

Cold stress is a major environmental factor affecting the growth, development, and productivity of various crop species. With the current trajectory of global climate change, low temperatures are becoming more frequent and can significantly decrease crop yield. Wheat (Triticum aestivum L.) is the first crop to be domesticated and is the most popular cereal crop in the world. Due to a lack of systematic research on cold response pathways and gene regulatory networks, the underlying molecular mechanisms of cold signal transduction in wheat are poorly understood. This study reviews recent progress in wheat, including the ICE-CBF-COR signaling pathway in cold stress and the effects of cold stress on hormonal pathways, reactive oxygen species (ROS), and epigenetic regulation. This review also highlights outstanding issues that are crucial for understanding the interactions between wheat and low-temperature conditions.

In perennial fruit crops, bearing can be influenced by various factors, including environmental conditions, germplasm, rootstocks, and cultivation methods. Cherries, one of the most important and popular fruit species from the temperate climate zone, achieve high prices on the market. New agricultural technologies and environmental factors force a change in the approach to cherry cultivation. Old-type cherry orchards with their high demand for water, nutrients and manual work are replaced by orchards of self-pollinating cherry cultivars grown on dwarf rootstocks. These changes make it necessary to search for ways to regulate fruiting, in particular to thin buds, flower and fruit. In view of environmental regulations and consumer pressure, thinning methods are being sought that either do not involve the use of chemicals or that use eco-friendly chemical agents. This review examines recent progress in understanding the effect of thinning methods on the physiology, tree growth and fruit quality of cherries, discusses horticultural practices aimed to ensure regular cropping and their influence on fruit quality, and provides suggestions for future research.

Occasionally, officials of the world’s regulatory agencies embark upon attempts at bringing previously unregulated physical systems under regulation by them. Each such attempt raises an epistemological issue. At issue is whether enough information about the outcomes of the events of the future, given the outcomes of the events of the present, will be in the hands of a would-be regulator for this regulator to regulate effectually. If present, this information is provided by runs of a model of the physical system that is slated for regulation. Ideally, this model makes an argument that draws its conclusion from the evidence presented to it. If so, this argument is of the form of a predictive inference. However, the process by which an argument draws its conclusion from the evidence may go awry. This happens, for example, when the axiom of probability theory called unit measure is falsified by a conclusion that is drawn from the evidence by this argument.A method is derived from first principles for determination of whether unit measure is satisfied or falsified by an argument made by a model, given that this argument may attach unusual meanings to statistical terms. This method is used in a study of whether unit measure is satisfied or falsified by the arguments that are made by a pair of models. Both models are in active use by regulatory agencies around the world. Under neither argument do runs of the model provide an official of a regulatory agency with the information gain aka mutual information that he or she would need to regulate effectually. Under both arguments, attachment of unusual meanings to statistical terms creates the illusion that such an official can and does regulate effectually.

Long noncoding RNA (lncRNA) are implicated in various genetic diseases and cancer, attributed to their critical role in gene regulation. RNA sequencing is used to capture their transcripts from certain cell types or conditions. For some studies, lncRNA interactions with other biomolecules have also been captured, which can give clues to their mechanisms of action. Complementary \textit{in silico} methods have been proposed to predict non-coding nature of transcripts and to analyze available RNA interaction data. Here we provide a critical review of such methods and identify associated challenges. Broadly, these can be categorized as reference-based and reference-free or \textit{ab initio}, with the former category of methods requiring a comprehensive annotated reference. The \textit{ab initio} methods can make use of machine learning classifiers that are trained on features extracted from sequences, making them suitable to predict novel transcripts, especially in non-model species. Machine learning approaches such as Logistic Regression, Support Vector Machines, Random Forest, and Deep Learning are commonly used. Initial approaches relied on basic sequential features to train the model, whereas the use of secondary structural features appears to be a promising approach for functional annotation. However, adding secondary features will result in model complexities, thus demanding an algorithm that can handle it and furthermore, considerably increasing the utilization of computation resources. Computational strategies combining identification and functional annotation which can be easily customized are currently lacking. These can be of immense value to accelerate research in this class of RNAs.

Evidence has been accumulated demonstrating that heavy metals may accumulate in various organs leading to tissue damage and toxic effects in mammals. In particular, the Central Nervous System (CNS) seems to be particularly vulnerable to cumulative concentrations of heavy metals, though the pathophysiological mechanisms is still to be clarified. In particular the potential role of oligodendrocyte dysfunction and myelin production after exposure to subtoxic concentration of heavy metals is to be better assessed. Here we investigated on the effect of sub-toxic concentration of several essential (Cu^{2 +}, Cr³⁺, Ni²⁺, Co²⁺) and non-essential (Pb²⁺, Cd²⁺, Al³⁺) heavy metals on MO3.13 and SHSY5Y human oligodendrocyte and neuronal cell lines (grown individually or in co-culture). In particular, exposure of both cell lines to heavy metals produced a reduced cell viability of co-cultured cell lines compared to cells grown separately. This effect was more pronounced in neurons which were more sensitive to metals than oligodendrocytes when the cells were grown in co-culture. On the other hand, a significant reduction of lipid component in cells occurred after their exposure to heavy metals, an effect accompanied by substantial reduction of the main protein that makes up myelin (MBP) in co-cultured cells. Finally, the effect of heavy metals in oligodendrocytes were associated to imbalanced intracellular calcium ion concentration as measured through the fluorescent Rhod-2 probe, thus confirming that heavy metals, even used at subtoxic concentrations, lead to dysfunctional oligodendrocytes. In conclusion, our data show, for the first time, that sub-toxic concentrations of several heavy metals lead to dysfunctional oligodendrocytes, an effect highlighted when these cells are co-cultured with neurons. The pathophysiological mechanism(s) underlying this effect is to be better clarified. However, imbalanced intracellular calcium ion regulation, altered lipid formation and, finally, imbalanced myelin formation seem to play a major role in early stages of heavy metal-related oligodendrocyte dysfunction.

Effortful control (EC) describes individual differences in self-regulation, with a strong attentional basis. Moreover, during early childhood EC has a central role on children’s socio-emotional adjustment and academic achievement. The aim of the current study was to predict the development of EC at 36 months of age from early attentional and environmental measures taken in infancy using a machine learning approach. A sample of 75 infants participated in a longitudinal study running different waves of data collection at 6, 9 and 36 months of age. Attentional tasks were administered at 6 months of age and two additional measures were collected at 9 months of age. Parents reported household environment variables during wave 1, and their child’s EC at 36 months. A machine -learning algorithm was implemented to identify children with low EC scores at 36 months of age. An “attention only” model showed greater predictive sensitivity than the “environmental only” model. However, a model including both attentional and environmental variables was able to classify the groups (Low-EC vs Average-to-High EC) with 100% accuracy. Sensitivity analyses indicate that socio-economic variables together with attention control processes at 6-months, and self-restraint capacity at 9-months, are the most important predictors of EC. Results suggest a foundational role of executive attention processes in the development of EC in complex interaction with household environment and provide a new tool to identify early markers of socio-emotional regulation development.

Keywords: conservation; cultural pluralism; environmental regulation; community-based natural resource management; Indigenous law

Keywords: Green human resource management1; Green supply chain management2; Regulation and legislation3; Sustainable development goals4.

Pesticides have a vital contribution to the agricultural industry in Australia. However, pesticide applications may not always selective to its target organism. Exposure to pesticide has been associated with negative impacts to human health. One of the ways to reduce pesticide risk to the population and the environment is through government regulations. To put Australia pesticide regulations into perspective, comparisons were made between Australia and other nation’s pesticides regulations. The EU pesticide regulatory system was chosen for comparison with the Australian’s in the aspect of protecting the population from pesticide exposure. The comparison showed that the assessment to authorize a pesticide in Australia is based on the risk while in the EU, the assessment is based on the hazard of the pesticide. A registered active substance in Australia can be authorized for use indefinitely unless it is nominated for reconsideration while the period of registration of an active substance in the EU lasts for 10 years. In addition, no routine systematic chemical residue surveys are conducted in Australia for food commodities. The results highlight areas for improvement in the Australian pesticide regulatory system from the perspective of controlling undue exposure among the general population.

Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. This plaque accumulation obstructs blood flow to the heart, resulting in a heart attack. While distinct features of CAD have been identified, its causes remain largely unclear, with the exception of environmental and nutritional factors. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in one-carbon metabolism. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T>C and 1170A>G genotypes with CAD susceptibility. We observed that TS 1100T>C polymorphisms increased disease susceptibility in several groups, while the TS 1170A>G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the 3'-UTR miRNA binding site of the TS gene could serve as clinically useful biomarkers for the prevention, prognosis, and management of CAD.

Plants are immobile, and, to overcome harsh environmental conditions, such as drought, salt, and cold, they have evolved complex signaling pathways. Abscisic acid (ABA), an isoprenoid phytohormone, is a critical signaling mediator that regulates diverse biological processes in various organisms. Significant progress has been made in the determination and characterization of key ABA-mediated molecular factors involved in different stress responses, including stomatal closure and developmental processes, such as seed germination and bud dormancy. Since ABA-signaling is a complex signaling network that integrates with other signaling pathways, the dissection of its intricate regulatory network is necessary to understand the function of essential regulatory genes involved in ABA signaling. In the present review, we focus on two aspects of ABA signaling. First, the perception of the stress signal (abiotic and biotic) and the response network of ABA-signaling components that transduce the signal to the downstream pathway to respond to stress tolerance, regulation of stomata, and ABA signaling component ubiquitination. Second, ABA-signaling in plant development processes, such as lateral root growth regulation, seed germination, and flowering time regulation. Examining such diverse signal integration dynamics could enhance our understanding of the underlying genetic, biochemical, and molecular mechanisms of ABA signaling networks in plants.

DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. Establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases: DNMT3A and DNMT3B, which are responsible for installing DNA methylation patterns during gametogenesis and early embryogenesis, and DNMT1, which is essential for propagating DNA methylation patterns during replication. Both groups of DNMTs are multi-modular proteins, containing a large N-terminal regulatory region in addition to the C-terminal methyltransferase domain. Recent structure-function investigations of the individual domains or large fragments of DNMT1 and DNMT3A have revealed the molecular basis for their substrate recognition and specificity, intramolecular domain-domain interactions, as well as their crosstalk with other epigenetic mechanisms. These studies highlight a multifaceted regulation for both DNMT1 and DNMT3A/3B, which is essential for the precise establishment and maintenance of lineage-specific DNA methylation patterns in cells. This review summarizes current understanding of the structure and mechanism of DNMT1- and DNMT3A-mediated DNA methylation, with emphasis on the functional cooperation between the methyltransferase and regulatory domains.

Digital machine intelligence has evolved from its inception in the form of computation of numbers to AI, which is centered around performing cognitive tasks that humans can perform, such as predictive reasoning or complex calculations. The state of the art includes tasks that are easily described by a list of formal, mathematical rules or a sequence of event-driven actions such as modeling, simulation, business workflows, interaction with devices, etc., and also tasks that are easy to do “intuitively”, but are hard to describe formally or as a sequence of event-driven actions such as recognizing spoken words or faces. While these tasks are impressive, they fall short in applying common sense reasoning to new situations, filling in information gaps, or understanding and applying unspoken rules or norms. Human intelligence uses both associative memory and event-driven transaction history to make sense of what they are observing fast enough to do something about it while they are still observing it. In addition to this cognitive ability, all bio-logical systems exhibit autopoiesis and self-regulation. In this paper, we demonstrate how machine intelligence can be enhanced to include both associative memory and event-driven transaction history to create a new class of knowledge-based assistants to augment human intelligence. The digital assistants use global knowledge derived from the Large Language Models to bridge the knowledge gap between various participants interacting with each other. We use the general theory of information and schema-based knowledge representation to create the memory and history of various transactions involved in the interactions.

Trait anxiety, emotion regulation strategies, and metacognitive beliefs influence executive functions (EF) and academic achievement. This study examines their interplay and impact on academic success. In total, 275 adolescents (10-17 years) and parents completed an online questionnaire assessing trait anxiety, emotion regulation strategies, metacognition, parent-reported behaviors related to executive functioning, and overall school average. Preliminary analyses confirmed consistency with existing literature for each variable and their interaction. Furthermore, we conducted a network analysis among the main variables. This analysis supports the need to pay more attention to reflective variables - maladaptive emotion regulation strategies and metacognitive beliefs about worry - when studying trait anxiety. These variables were linked to problematic executive functioning in adolescents. These latter had a negative link to academic achievement. This study offers innovative insights by investigating less-explored relationships in the scientific literature. It reveals high and significant correlations between metacognitive beliefs, maladaptive emotion regulation strategies and trait anxiety (r > .500, p < .001) but also between these variables and both executive functioning and academic achievement. These findings offer new perspectives for research and underscore the importance of holistically examining psychological factors related to academic success.

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e thiazolidinedione (TZD) class of drugs on Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and NOR mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independant mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies.

It has long been known that phytohormone auxin plays a promoting role in tuber formation and stress tolerance in potatoes. Our study aimed to identify and characterize the complete sets of auxin-related genes that presumably constitute the entire auxin signaling system in potato (Solanum tuberosum L.). The corresponding genes were retrieved from sequenced genomes of the doubled monoploid S. tuberosum DM1-3-516-R44 (DM) of the Phureja group, the heterozygous diploid line RH89-039-16 (RH), and the autotetraploid cultivar Otava. Both canonical and noncanonical auxin signaling pathways were considered. Phylogenetic and domain analyzes of deduced proteins were supplemented by their expression profiling and 3D molecular modeling. The canonical and ABP1-mediated pathways of auxin signaling appeared to be well conserved. Total number of potato genes/proteins presumably involved in canonical auxin signaling is 46 and 108 in monoploid DM and tetraploid Otava, respectively. Among studied potatoes, spectra of expressed genes obviously associated with auxin signaling were partly cultivar-specific and quite different from analogous spectrum in Arabidopsis. Most of the noncanonical pathways found in Arabidopsis appeared to be low probable in potato. This was equally applied to all cultivars used irrespective of their ploidy. Thus, some important features of the (noncanonical) auxin signaling pathways may be variable and species-specific.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSD), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role of immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Ethylene is an essential plant hormone critical in various physiological processes. These processes include seed germination, leaf senescence, fruit ripening, and the plant's response to environmental stressors. Ethylene biosynthesis is tightly regulated by two key enzymes, namely 1-aminocyclopropane-1-carboxylate synthase (ACS) and 1-aminocyclopropane-1-carboxylate oxidase (ACO). Initially, the prevailing hypothesis suggested that ACS is the limiting factor in the ethylene biosynthesis pathway. Nevertheless, accumulating evidence from various studies has demonstrated that ACO, under specific circumstances, acts as the rate-limiting enzyme in ethylene production. Under normal developmental processes, ACS and ACO collaborate to maintain balanced ethylene production, ensuring proper plant growth and physiology. However, under abiotic stress conditions, such as drought, salinity, extreme temperatures, or pathogen attack, the regulation of ethylene biosynthesis becomes critical for plants’ survival. This review highlights the structural characteristics, examines the transcriptional, post-transcriptional, and post-translational regulation of ACS and ACO, and their role under abiotic stress conditions. Reviews on the role of ethylene signaling in abiotic stress adaptation are available. However, a review that delineates the role of ACS and ACO in abiotic stress acclimation is not available.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

In the context of the coordinated development of digital economy and environmental protection, we take the strategy of "Broadband China" as a quasi-natural experiment, adopts the panel data of 284 cities from 2007 to 2020, and evaluates the policy effect of digital economy on total factor energy efficiency through the progressive DID model. The results show that: The construction of "Broadband China" demonstration city has significantly promoted the improvement of the total factor energy efficiency of the demonstration city, but there is also significant urban heterogeneity, which is manifested in the significant improvement of the total factor energy efficiency of the eastern city, the southern city, the big city and the non-resource-based city. It has no significant effect on the total factor energy efficiency of central and western cities, northern cities, small and medium-sized cities and resource-based cities. The construction of "Broadband China" demonstration cities can improve total factor energy efficiency by promoting technological progress and strengthening environmental regulations. Therefore, we should further strengthen the construction of digital infrastructure and give full play to its positive effects. Different cities should seek differentiated development paths based on their own resource endowments and development conditions, so that the digital economy can effectively improve the total factor energy efficiency.

Prostate cancer (PC) is a common malignancy of elderly men, characterized by great heterogeneity in its clinical course, ranging from an indolent to a highly aggressive disease. The aggressive variant prostate cancer (AVPC) clinically shows an atypical pattern of disease progression, similar to that of small cell PC (SCPC), and also shares the chemo-responsiveness of SCPC. The term AVPC does not describe a specific histologic subtype of PC but rather the group of tumors that, irrespective of morphology, show an aggressive clinical course, dictated by androgen receptor (AR) indifference. AR indifference represents an adaptive response to androgen deprivation therapy (ADT), driven by epithelial plasticity, an inherent ability of tumor cells to adapt to their environment by changing their phenotypic characteristics in a bi-directional way. The molecular profile of AVPC entails combined alterations in tumor suppressor genes retinoblastoma protein 1 (RB1), tumor protein 53 (TP53) and phosphatase and tensin homolog (PTEN). The understanding of the biologic heterogeneity of castration-resistant PC (CRPC) and the need to identify the subset of patients that would potentially benefit from specific therapies necessitate the development of prognostic and predictive biomarkers. This review aims to discuss the possible pathophysiologic mechanisms of AVPC development and the potential use of emerging tissue-based biomarkers in clinical practice.

Background: Identity diffusion plays a central role in the onset of borderline personality and disorders. The Dialectical Behavioral Therapy for Adolescents (DBT-A) is a treatment program for adolescents with emotional instability and dysregulation. The interest of this study is to examine the influence of a standardized and certified DBT-A therapy program on identity development of adolescents with emotion dysregulation in an inpatient setting. Methods: 138 adolescents aged 13 to 18 years with symptoms of emotional instability were assessed before and after a curricular 12-weeks in-patient DBT-A program with standardized instruments for the assessment of identity (AIDA), emotion regulation (FEEL-KJ, SEE) and general psychopathology (SCL-90-R, DIKJ). Results: The results indicate a significant change in identity development, emotion regulation and general symptoms of psychopathology after treatment with DBT-A. A connection between identity scales and psychopathological symptoms of adolescents with diagnosed borderline disorders and impaired emotion regulation could be established. Conclusion: In this large sample of adolescents, DBT-A significantly improved identity and reduced identity diffusion. As identiy disturbance is a core symptom of borderline personality disorder, our results may become clinically relevant for the prevention of personality disorders in emotionally unstable adolescents

Air pollution is an important factor affecting human health and daily life. Chinese government is making vigorous efforts to control air pollution. The upgrading of industrial structure is a problem-solving tool in environment and economic growth cases. This paper aims to explore the relationships among environmental regulation, the upgrading of industrial structure and air pollution. The PVAR (Panel Vector Auto Regression) model and moderation effect model has been used to conduct empirical analysis based on panel data of 30 provinces in China from 2004 to 2020. The results of analysis indicate (1) the environmental regulation can significantly reduce the air pollution, but the deterioration of air quality could not effectively influence environmental regulations. (2) The upgrading of industrial structure can weaken the air pollution and air pollution hinders the upgrading of industrial structure. (3) With the improvement of environmental regulation, the industrial structure is constantly upgraded, but the upgrading of the industrial structure has a negative effect on the improvement of environmental regulation. (4) The upgrading of industrial structure can positively moderate the influence of environmental regulation on air pollution.

Solar energy (SE) is essential for decarbonization of our economy and for energetic transition. Solar energy can be a sustainable economic activity as long as a balance is struck between the benefits it brings to climate change mitigation and the damage it can cause to biodiversity and ecosystems. Here we study this balance in an area with high biodiversity under pressure for installation of numerous photovoltaic plants (PPs). Our results show that developers give priority to the cheapest land close to connection points, while other values (e.g., environmental, landscape) are secondary. The regulatory process carried out by the Administration does not ensure the preservation of natural values, as several PPs with a high impact on important conservation areas have been approved. Experts' allegations provide quality information to the Administration to evaluate and demand changes to the projects presented. Such demands show that companies are willing to relocate plants to land occupied by olive groves. In this way, greater efficiency is achieved in land occupation, as well as shorter evacuation lines, water savings and less environmental impact. Prior strategic territorial planning could have avoided the impact of PPs already built, made the deployment of new PPs compatible with biodiversity conservation, and contributed to improving the management of key resources, such as subway aquifers. The proposed regulatory changes to the environmental assessment procedure (exclusion of renewables and public participation from the procedure) are detrimental, as they will make SE unable to meet the requirements of the Taxonomy Regulation.

Wildlife conservation is an important component of environmental sustainability and can be improved by reviewing the performance of its three major models – common pool, top-down regulatory, and private resource -- under varying environmental and socioeconomic conditions. Generally, the private resource model is the most sustainable because it provides the best incentives to balance the needs of humans and wildlife, to maintain general wildlife habitat, and to adapt quickly to changing environmental and/or socioeconomic conditions. Top-down or “command and control” regulation, however, can be employed as a model of last resort if the private resource model shows signs of failing to protect specific species from local extirpation or extinction, which it is most likely to do for migratory species, species with close commercial substitutes, and species with no direct commercial value. Top-down regulators may also be needed to enforce property rights arrangements like catch shares and to monitor resources that remain in the common pool in the event that socioeconomic or environmental conditions change sufficiently to trigger the tragedy of the commons.

Computational simulation using mathematical models is a useful method for understanding the complex behavior of a living system. The majority of studies using mathematical models to reveal biological mechanisms uses one of the two main approaches: the bottom-up or the top-down approach. When we aim to analyze a large-scale network, such as a comprehensive knowledge-integrated model of a target phenomenon, for example a whole-cell model, the variation of analyses is limited to particular kind of analysis because of the size and complexity of the model. To analyze a large-scale regulatory network of neural differentiation, we developed a hybrid method that combines both approaches. To construct a mathematical model, we extracted network motifs, subgraph structures that recur more often in a metabolic network or gene regulatory network than in a random network, from a large-scale regulatory network, detected regulatory motifs among them, and combined these motifs. We confirmed that the model reproduced the known dynamics of HES1 and ASCL1 before and after differentiation, including oscillation and equilibrium of their concentrations. The model also reproduced the effects of overexpression and knockdown of the Id2 gene. Our model suggests that the characteristic change in HES1 and ASCL1 expression in the large-scale regulatory network is controlled by a combination of four feedback loops, including a large loop which has not been focused on. The model extracted by our hybrid method has the potential to reveal the critical mechanisms of neural differentiation. The hybrid method is applicable to other biological events.

The differential gear train and speed regulating motor constitute the variable ratio transmission for grid-connected wind turbine with differential speed regulation. The synchronous generator in the system can accessing the power grid without frequency converter. The transmission can realize the mode of variable speed constant frequency that the wind rotor speed is varying and the generator rotor speed is constant. The power control method is studied under the different wind speed which is lower or higher than rated wind speed with using the relational expression of utilization rate of wind energy Cp, pitch angle β and the tip speed ratio λ. The SIMULINK software is used to build the 1500 kW wind turbine model with differential speed regulation. Some different wind speed is made as input. The feasibility of power control method for grid-connected wind turbine with differential speed regulation is verified by the comparison between the simulation results and the theoretical value of the key parameters.

Batteries are called to be part of the electricity grid by providing ancillary services. Area regulation services seem to provide substantial revenues and profit. But Li-ion batteries are still too expensive to enter widely into this market. On the other hand, electric vehicle batteries are considered inappropriate for traction purposes when they reached a state of health of 80%. The reuse of these batteries offers affordable batteries for second life stationary applications. This study analyzes how batteries may provide services to a gas turbine cogeneration power plant and how long these batteries may last under different loads.

A growing number of companies in the brewery industry have made commitments to measure and reduce their greenhouse gas (GHG) emissions. However, many brewers, particularly craft brewers with relatively low rates of production, have struggled to meet these commitments. The purpose of this research was to investigate the challenges and benefits of measuring and reducing GHG emissions in the craft brewery industry. The research was conducted in Ontario, Canada, which has seen strong recent growth in the craft brewery industry. A case study and semi-structured interviews among Ontario Craft Brewers were conducted. The case study found that indirect (scope 3 emissions under the WBCSD & WRI GHG Protocol) GHG sources accounted for 46.4% of total GHGs, with major sources from barley agriculture, malted barley transportation, and bottle production. Direct emissions (scope 1) accounted for only 14.9% of GHGs, while scope 2 emissions, comprised mainly of energy consumption, accounted for 38.7% of GHGs. The case study and interviews found that the main challenges in calculating brewery GHGs are secondary data availability, technical knowledge, and finances. The study also found that the main benefits for Ontario breweries to measure their GHGs include sustainability marketing and preserving the environment. The interviews also found a poor understanding of carbon regulation among Ontario Craft Brewers, which is interesting considering that Ontario implemented a provincial cap and trade program in 2017.

The cucumber mosaic virus (CMV) 2b protein is a suppressor of plant defenses and a pathogenicity determinant. Amongst the 2b protein’s host targets is the RNA silencing factor Argonaute 1 (AGO1), which it binds to and inhibits. In Arabidopsis thaliana, if 2b-induced inhibition of AGO1 is too efficient it induces reinforcement of antiviral silencing by AGO2, and triggers increased resistance against aphids, CMV’s insect vectors. These effects would be deleterious to CMV replication and transmission, respectively, but are moderated by the CMV 1a protein by sequestering sufficient 2b protein molecules into P-bodies to prevent excessive inhibition of AGO1. Mutant 2b protein variants were generated and red and green fluorescent protein fusions used to investigate subcellular colocalization with AGO1 and the 1a protein, and the effects of mutations on complex formation with the 1a protein and AGO1 were investigated using bimolecular fluorescence complementation and co-immunoprecipitation assays. Although we found that residues 56-60 influenced the 2b protein’s interactions with the 1a protein and AGO1, it appears unlikely that any single residue or sequence domain is solely responsible. In silico predictions of intrinsic disorder within the 2b protein secondary structure were supported by circular dichroism (CD) but not by nuclear magnetic resonance (NMR) spectroscopy. Intrinsic disorder provides a plausible model to explain the 2b protein’s ability to interact with AGO1, the 1a protein and other factors. However, the reasons for the conflicting conclusions provided by CD and NMR must first be resolved.

This study examines the environmental challenges faced by Malaysian industries in adhering to industrial effluent regulations with the research question, what are the challenges in complying with environmental legislations from industries? It investigates the primary factors contributing to non-compliance and the perspectives, knowledge, and needs of Malaysian industries regarding environmental compliance. This study recommends the best strategy for promoting self-compliance. Thirteen stakeholders from various industries with environmental management experience were interviewed. Over the past seven years, these industries have shown low com-pliance with the Industrial Effluent Regulation 2009, prompting an exploration of their adaptability to regulations. Challenges identified include cost, employee attitudes, technology, management support, public complaints, and jurisdictional issues. Responses varied from divergent to unified viewpoints, highlighting the complexity of compliance issues. Respondents suggested enhancing compliance through behavioral changes, including incentives, enforcement, awareness, guidance, industry ratings, management commitment, and public disclosure of emissions. Suggestions for improvement and innovative solutions emerged based on participants' experiences, emphasizing the importance of continuous improvement. The study emphasizes the government's crucial role in ensuring regulation adherence but underscores the need for analyzing barriers and exploring alternative approaches. Understanding industry perspectives and strategies is essential for progress. Compliance, however, requires an analysis of the current challenges and adopting adaptive measures. It is important to understand industries' perspectives and strategies to move forward.

Measuring the impact of land use regulation on the land market involves identifying and classifying relevant impact factors related to the land market. The objective of this study was to identify land market impact factors in the context of the introduction of land use regulation in Nepal. A desktop review was carried out to identify preliminary set of impact factors, which were reclassified through intuitive analysis based on the degree of thematic closeness. Perspective-based impact factors were identified through the qualitative analysis of primary data collected through semi-structured interviews with the Nepalese land market stakeholders. These independently derived impact factors were compared with the desktop literature review impact factors resulting in fourteen land market impact factors across four dimensions, including transaction cost, valuation, mortgage availability, taxation, and compensation across the economic dimension; lot size, subdivision restrictions, and coordination across the institutional dimension; awareness, expectation and proximity across the social dimension; and risk reduction, quality of residential land, and suitability of zoning classification across the environmental dimension. There was significant overlap and commonality across factors identified from both the literature review and semi-structured interviews. The land market impact factors determined in the study may be adapted and generalized across other countries and could be utilized to better understand the impacts of land policy decisions on urban planning and development. Further research is recommended on the process to operationalize the use of these factors to quantify the impact of land use regulation on different land markets.

The device and method in accordance with the constant pressure regulation of micro droplet PCR in microfluidic chips are developed to explore the optimization way for the micro droplet movement, fragmentation, and bubble generation in microfluidic chips in existing digital PCR technology. In the developed device, an air source device is adopted to regulate the pressure in the chip, such that micro droplet generation and PCR amplification without bubbles can be achieved. In 3 min, the sample in 20ul will be distributed into nearly 50,000 water-in-oil droplets exhibiting a diameter of about 87μm, and the micro droplet will be subjected to a close arrangement in the chip without air bubbles. The device and chip are adopted to quantitatively detect the human gene . As indicated by the experimental results, a good linear relationship exists between detection signal and DNA concentration ranging from 101~ 105 copies /μL (R2=0.999). The micro droplet PCR devices based on constant pressure regulation chips exhibit a wide variety of advantages (e.g., achieving high pollution resistance, micro droplet fragmentation and integration avoidance, reducing human interference, and standardizing results). Thus, micro droplet PCR devices based on constant pressure regulation chips have promising applications in nucleic acid quantification.

Low-temperature accumulation is one of the essential stages in the growth process of woody ornamental plants. In this study, two different low-temperature treatments, 6℃ and 10℃, were used to analyze the effects of different low-temperature treatments on dormancy release and flowering of the 'Gulihong' plant using artificial low temperatures. Based on the experimental results, four typical early-blooming Prunus mume cultivars widely planted in Yangling area of Henan Province, China, including 'Zaoyudie', 'Zaohualve', 'Nanjing gongfen', and 'Gulihong', were selected as the experimental materials. The effects of low-temperature accumulation on the flowering characteristics of different cultivars were analyzed using a 6℃ artificial low-temperature treatment. The suitable cultivation temperature for early-blooming P. mume cultivars was screened to provide a theoretical basis for further exploration of P. mume bonsai cultivation techniques. The results showed that the flowering rate, flower diameter, flowering quantity, flowering uniformity, and bud development in the 6℃ treatment were significantly better than those in the 10℃ treatment. The flowering rate and quality of different cultivars gradually increased with the accumulation of low-temperature. Therefore, chill accumulation plays a significant role in promoting flowering quality.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people. Under constant exposure to highly dynamic environmental cues in diverse host niches, C. albicans has successfully evolved to adapt to both commensal and pathogenic lifestyles. The ability of C. albicans to undergo a reversible morphological transition from yeast to filamentous forms is a well-established virulent trait. Over the past few decades, a significant amount of research has been carried out to understand the underlying regulatory mechanisms, signaling pathways, and transcription factors that govern the C. albicans yeast-to-hyphal transition. This review will summarize our current understanding of well-elucidated signal transduction pathways that activate C. albicans hyphal morphogenesis in response to various environmental cues and the cell cycle machinery involved in the subsequent regulation and maintenance of hyphal morphogenesis.

RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found in silico evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway through interaction with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51 binding sites in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-binding sites in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway were significantly occupied by RAD51 in all four cell lines. Taken together, these results predicted a novel role of RAD51 that had not been addressed previously, and provided evidence that RAD51 could possibly be involved in regulating genes associated with the autophagy pathway, through interaction with E-box binding proteins.

The mobile devices caused a constant struggle for the pursuit of data privacy. Nowadays, it appears that the number of mobile devices in the world is increasing. With this increase and technological evolution, thousands of data associated with everyone are generated and stored remotely. Thus, the topic of data privacy is highlighted in several areas. There is a need for control and management of data in circulation inherent to this theme. This article presents an approach of the interaction between the individual and the public environment, where this interaction will determine the access to information. This analysis was based on a data privacy management model in public environments created after reading and analyzing the current technologies. A mobile application based on location via Global Positioning System (GPS) was created to substantiate this model, which it considers the General Data Protection Regulation (GDPR) to control and manage access to the data of each individual.

Direct-to-consumer genetic testing companies aim to predict the risks of complex diseases using proprietary algorithms. Companies keep algorithms as trade secrets for competitive advantage, but a market that thrives on the premise that customers can make their own decisions about genetic testing should respect customer autonomy and informed decision making and maximize opportunities for transparency. The algorithm itself is only one piece of the information that is deemed essential for understanding how prediction algorithms are developed and evaluated. Companies should be encouraged to disclose everything else, including the expected risk distribution of the algorithm when applied in the population, using a benchmark DNA dataset. A standardized presentation of information and risk distributions allows customers to compare test offers and scientists to verify whether the undisclosed algorithms could be valid. A new model of oversight in which stakeholders collaboratively keep a check on the commercial market is needed.

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing, and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3’ UTR, 5’ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved, and how sRNAs integrate with complex regulatory networks.

During the last decades, zebrafish (Danio rerio) has become one of the most important model organisms to study different physiological and biological phenomena. Research field of carbonic anhydrases (CAs) and carbonic anhydrase related proteins (CARPs) is not an exception in this. The best-known known function of CAs is the regulation of acid-base balance. However, studies performed with zebrafish, among others, have revealed important roles for these proteins in many other physiological processes, some of which have been unpredicted in the light of the previous studies and suggestions. Examples are roles in zebrafish pigmentation as well as motor coordination. Disruption of the function of these proteins may generate even lethal outcomes. In this review, we summarize the current knowledge of CA-related studies performed in zebrafish.

Drought is one of the most serious abiotic stressors in the environment, restricting agricultural production by reducing plant growth, development, and productivity. To investigate such a complex and multifaceted stressor and its effects on the plants, a systems biology-based approach is necessitated, entailing the generation of co-expression networks, identification of highly-priority transcription factors (TFs) dynamic mathematical modeling, and computational simulations. Here, we studied a high-resolution drought transcriptome of Arabidopsis. We revealed distinct temporal transcriptional signatures and demonstrated the involvement of specific biological pathways. Generation of a large-scale co-expression network followed by network centrality analyses identified 117 TFs that possess critical properties of hubs, bottlenecks, and high clustering coefficients nodes. Dynamic transcriptional regulatory modeling on integrated TF-target and transcriptome datasets uncovered major transcriptional events during the course of drought stress. Mathematical transcriptional simulations allowed us to ascertain the activation status of major TFs as well as the transcriptional intensity and amplitude of their target genes. Finally, we validated our predictions by providing experimental evidence of gene expression under drought stress for a set of four TFs and their major target genes using qRT-PCR. Taken together, we provided a systems-level perspective on the dynamic transcriptional regulation during drought stress in Arabidopsis and uncovered numerous novel TFs that can potentially be used in future genetic crop engineering programs.

Leishmania species are parasitic protozoans which cause leishmaniasis affecting millions of people worldwide. Sterols are important components of plasma and organellar membranes and serve as precursors for the synthesis of signaling molecules. In contrast to animals, Leishmania do not produce cholesterol but instead synthesize ergostane-based sterols. C14-demethylase is a key enzyme involved in the biosynthesis of sterols in Leishmania parasites and an important drug target. Its inactivation leads to multiple defects including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis plays an unexpected role in global gene regulation in Leishmania parasites.

(1) The present study investigated the effect of orally administered Limosilactobacillus fermentum HY7302 (HY7302) on the relationship between ocular tissue and the microbiome in the corneal injured dry eye mice model. (2) 0.1% benzalkonium chloride (BAC) was applied to the ocular surface for 14 days to induce corneal injury in male Balb/c mice. During the BAC treatment period, HY7302 (1 × 108 CFU/kg/day or 1 × 109 CFU/kg/day) or omega-3 positive control (200 mg/kg/day) were administered orally (n = 8/group). To examine signaling pathways affected by HY7302 treatment, the in vitro effects of HY7302 on tight junctions and the inflammatory response were investigated in a mouse colon epithelial cell line, CMT-93. (3) BAC exposure decreased tear production, induced ocular inflammation and corneal epithelial detachment, and altered gut microbiota. However, oral administration of HY7302 restored tear secretion and decreased corneal epithelial detachment in BAC-treated corneal injury mice. Further, HY7302 alleviated corneal inflammation via modulation of matrix metalloproteinase-9 (MMP-9) expression and alterations in gut microbiota composition. (4) These findings suggest that the gut–eye axis interaction between gut microbiota and eye tissue affects disease severity in corneal injury, and that alteration of the microbiota by HY7302 could improve eye health by regulating the inflammatory response.

Anemia and thyroid disorders are global health issues that affect all ages but are more apparent in women. In this case, some serological components responsible for IDA and TSH disorders in women have been found actively regulated through a complex steroidal-calcitriol mediated pathway. This research has been investigated the correlation between Calcitriol and the serological components responsible for IDA and TSH disorders in childbearing and non-child-bearing women of different health conditions. Experimental sampling from 452 women suffering from both IDA and TSH disorders were taken, aged between 0 and 70 years. Serological parameters, such as iron, total iron-binding capacity and ferritin, were assessed for IDA profiling, whereas thyroid-stimulating hormone and free thyroxin were for TSH profiling based on the individual’s serum calcitriol status. The resulted serological data were interpreted using sophisticated computer programming language and algorithms for quantitative biochemical analysis. The study resulted in a significant correlation between FT4 and Calcitriol (P<0.0001) for all age groups. TSH also showed strong interactions with the fluctuation of calcitriol level (P<0.0001), except for the children aged below 10 years (P<0.063). The iron, TIBC, TSH, and FT4 showed phenomenal regulation with the steroidal-calcitriol concentration for congenital patients. Unlike the others, ferritin has a substantial connection with Calcitriol (P<0.0064) fluctuation in the serum. To ratify, the concentrations of TSH, FT4, iron, TIBC, and ferritin were found to be significantly interconnected in terms of serum calcitriol level in women suffering from IDA and TSH disorders simultaneously. To understand the accuracy and efficacy of the Calcitriol in IDA and TSH disorders, some other inflammatory markers and parathyroid hormone analysis are need in future studies, besides a large number of samples.

Gut luminal dysbiosis and pathobiosis result in compositional and biodiversify alterations in the microbial and host co-metabolites. The main mechanism of bacterial evolution is horizontal gene transfer (HGT) and acquisition of new traits can be achieved through mobile genetic element (MGEs) exchange. Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by GEMs' horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to august 2023, using appropriate MeSH entry terms were performed. GEMs' horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cells inhabitants. The worldwide regulatory authority's safety control of GEMs is not enough to protect public health. Viability and biocontainment and many other aspects are only partially controlled and harmful consequences for public health should be avoided. Always remember that prevention is the most cost- effective strategy and "primum non nocere" is the name of the game.

Following the adoption of the Kunming-Montreal Global Biodiversity Framework (KM-GBF), with the Convention on Biological Diversity serving as its guiding treaty, the European Union (EU) has just reached an agreement on an EU Nature Restoration Regulation. This study carries out a systematic cross-walk between the restoration regulation and the KM-GBF, focusing on their implications for forest ecosystems. This paper identifies areas of alignment, divergence, and potential gaps related to habitat restoration, species protection, climate resilience, and the sustainable use of natural resources. The methodology adopts a grounded approach, starting with the 23 targets outlined in the KM-GBF and proceeding to the 28 articles set out in the restoration regulation. The results highlight the need for better alignment between the KM-GBF, the restoration regulation, and other forest-relevant EU policy instruments. The study stresses the need for a coherent and integrated EU policy approach that can address the diverse challenges and policy objectives facing forests. It concludes that amendments to the restoration regulation have significantly diluted its potential impact, limiting the EU Members States accountability and ability to meet KM-GBF goals and targets. It further stresses the need for strategies that can reconcile divergent EU policy pathways, support forest management and restoration efforts, while aligning with global biodiversity objectives.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Research in various fields of evolutionary biology has shown that divergence in gene expression is a key driver for phenotypic variation. An exceptional contribution of cis-regulatory evolution has for instance been found to contribute to morphological diversification. In the light of these findings, the analysis of genome-wide expression data has become one of the central tools to link genotype and phenotype information on a more mechanistic level. However, in many studies, especially if general conclusions are drawn from such data, a key feature of gene regulation is often neglected. With our article, we want to raise awareness that gene regulation and thus gene expression is highly context dependent. Genes show tissue- and developmental stage-specific expression. We argue that the regulatory context must be considered when studying evolution of gene expression.

High-penetration of Distributed Energy Resources (DER) in low voltage distribution grids, mainly photovoltaics (PV), might lead to overvoltage in the point of common coupling. Volt-VAr is one of the common control functions for DER power converters used to enhance the stability and the reliability of the voltage in the distribution system and, thus, fulfilling the network operator requirements. In this study, a centralized algorithm will provide local Volt-VAr control parameters to each PV inverter, based on the electrical grid characteristics where each equipment is installed. Since accurate information of grid characteristics is typically not available, the parametrization of the electrical grid is done using power meter data in DER location and a voltage sensitivity matrix. The algorithm has different optimization modes to both minimize voltage deviation and line current. In order to validate the effectiveness of the algorithm and its deployment in real infrastructure, it has been tested in an experimental setup with PV emulators in a set of 5-day tests. Volt-VAr control algorithm successfully adapted its parameters based on grid topology and PV inverter characteristics, achieving a voltage reduction up to 25% of the allowed voltage deviation.

This review article offers an in-depth look at DNA, its discovery, structure, functions, and the significant role it plays in modern biomedical research. It begins by revisiting the landmark discovery of the DNA double helix by scientists Watson and Crick, a structure resembling a twisted ladder that forms the blueprint of life. The review explains the basic processes of DNA replication (copying DNA), transcription (converting DNA to RNA), and translation (turning RNA into proteins), which are fundamental to understanding how genetic information is passed on and used by living organisms. The article then explores gene regulation and epigenetics, which involve how genes are turned on or off and how environmental factors can affect gene expression without changing the DNA sequence itself. It examines how DNA interacts with various proteins and modifiers, which play crucial roles in these processes. A major focus is on the advancements in DNA sequencing technologies. From the initial Sanger sequencing method, which was labor-intensive and time-consuming, to the highly efficient next-generation sequencing (NGS) and the latest single-molecule sequencing techniques, the review covers how these technologies have revolutionized genomics and personalized medicine. It also highlights the importance of computational genomics and bioinformatics, fields that deal with analyzing and interpreting the vast amounts of data generated by DNA sequencing. The review discusses DNA's crucial role in understanding human diseases. It covers DNA-based research in cancer, rare genetic disorders, infectious diseases, and pharmacogenomics (how genes affect a person's response to drugs). It emphasizes studies that have led to new ways of diagnosing and treating diseases. The article looks at the future of DNA research. It talks about emerging technologies like CRISPR-Cas9, a revolutionary gene-editing tool that allows scientists to modify DNA with high precision. Synthetic biology, an interdisciplinary field that combines biology and engineering for designing and constructing new biological parts and systems, is also discussed. Furthermore, DNA nanotechnology, which involves designing DNA molecules for technological uses, is explored. Finally, the review addresses ethical issues in DNA research, such as privacy concerns and debates over genome editing.

Amyotrophic lateral sclerosis (ALS) is also called "motor neuron disease”. In this review, we propose that ALS is not just a neuromotor disorder, but begins as a disorder of P53-modulated skeletal muscle metabolism, leading to failures at the energy state of the cells, incorrect redox states, motor denervation, and a loss of muscle fibers. Motoneurons die as a consequence of the lack of muscular feedback, and the oligomeric TDP43 aggregates progressively and relentlessly lead to mistakes in peripheral immune self-tolerance sustained over time. An effective treatment has not been found for this devastating pathology, as for 152 years the target has not been accurately defined. Scientists and doctors should consider new knowledge regarding ALS and consider immunomodulatory therapies that, based on genetic analysis and symptoms, can be combined with compounds that regulate metabolism and promote the elimination of useless organelles and cells. What if ALS could be cured as a result of seeing motor neuron disease differently? This review aims to develop that goal and change the paradigm of our understanding of ALS.

Entamoeba histolytica, the causative agent of amebiasis, is the third leading cause of death among parasitic diseases globally. Its life cycle includes encystation, which has been mostly studied in Entamoeba invadens, responsible of reptilian amebiasis. However, the molecular mechanisms underlying this process are not fully understood. Therefore, we focused on the identification and characterization of Myb proteins, that regulate the expression of encystation-related genes in various protozoan parasites. Through bioinformatic analysis, we identified 47 genes in E. invadens encoding MYB-domain-containing proteins. These were classified into single-repeat 1R (19), 2R-MYB proteins (27), and one 4R-MYB protein. The in silico analysis suggests that these proteins are multifunctional, participating in transcriptional regulation, chromatin remodeling, telomere maintenance, and splicing. Transcriptomic data analysis revealed expression signatures of eimyb genes, suggesting a potential orchestration in the regulation of early and late encystation-excystation genes. Furthermore, we identified 3135 probable target genes associated with reproduction, meiotic cell cycle, ubiquitin-dependent protein catabolism, and endosomal transport. In conclusion, our findings suggest that E. invadens Myb proteins regulate stage-specific proteins and a wide array of cellular processes. This study provides a foundation for further exploration of the molecular mechanisms governing encystation and unveils potential targets for therapeutic intervention in amebiasis.

This article summarizes Chinese framework for regulating artificial intelligence and integrates evolutionary game theory with cost-benefit analysis to establish a model and simulation. This framework is employed to analyze the behavioral trends among three distinct entities: governmental bodies, third-party independent institutions, and AI companies within the context of regulatory relationship. The findings indicate that: (1) The cost-benefit dynamics within the regulatory legal nexus significantly influence the behaviors of these entities; (2) Under the condition of normalized government regulation approaching full enforcement, the behavioral choices of third-party independent institutions and AI companies exhibit cyclical fluctuations.The paper draws two principal conclusions: (1) The regulatory framework need to be tailored to the specific risks presented by AI and the relative costs and benefits of legal enforcement in different jurisdictions. (2) From a cost-benefit standpoint, government intervention in AI regulation ought to be circumscribed, with government regulation focusing on critical legal risks. Other aspects of regulatory control should be delegated to cooperative legal framework that allows the participation of the independent third-party institution,which brings a nuanced and specialized approach to the governance of AI.

The MMP-9-1562C/T polymorphism influence incidence and course of many diseases of the central nervous system. We found, using luciferase assays and Q-RT-PCR technique, allele-specific in-fluence of MMP-9-1562C/T polymorphism on the MMP-9 promoter activity and on the expression of MMP-9 mRNA in human neurons derived from SH-SY5Y cells. Then, we have elucidated the mechanism responsible for the allele-specific action of the MMP-9-1562C/T polymorphism on transcriptional regulation of the MMP-9 gene using pull-down assay combined with mass spec-trometry analysis, EMSA and EMSA supershift techniques, as well as DsiRNA-dependent gene silencing. We have found that MMP-9 promoter activity and MMP-9 mRNA expression are reg-ulated in human neurons in the MMP-9-1562C/T allele-specific manner with stronger upregulation conferred by the C allele. Moreover, we have revealed that the allele-specific action of the MMP-9-1562C/T polymorphism on the neuronal MMP-9 expression is related to HDAC1 and ZNF384 transcriptional regulators. We show that HDAC1 and ZNF384 bind differentially to the C and the T alleles forming in vitro different regulatory complexes. Moreover, our data demonstrate that HDAC1 and ZNF384 downregulate differentially the MMP-9 gene promoter activity and MMP-9 mRNA expression in vivo in human neurons acting mostly via the T allele.