Primary Regulator Research Articles

LAW ENFORCEMENT ON THE CRIMINAL ACTS OF SERIOUS ABUSE BY CHILDREN TO CHILDREN ACCORDING TO LAW NUMBER 35 OF 2014 ON CHILD PROTECTION

This study aims to analyze the qualifications of criminal acts of physical violence against children based on legislation and to analyze the application of criminal law in criminal acts of physical violence against children in Decision Number 19/Pid.Sus-Anak/2018/PN Jkt.Pst., and Decision Number 00/Pid.Sus-Anak/2023/PN Jkt.Brt. The type of research used by the author is a type of normative legal research with a legislative approach method, a case approach, and a conceptual approach. The legal materials used consist of primary legal materials, namely laws and regulations, and judges' decisions. Secondary legal materials, namely journals and book literature related to this study. As well as tertiary legal materials, namely articles and literature on the internet as supporting data in this study. All of these legal materials are analyzed qualitatively and presented descriptively. The results of this study are, 1) The qualification of the crime of physical violence against children based on statutory regulations is an act that is included in Article 80 Paragraph (1) of Law Number 35 of 2014 concerning Amendments to Law Number 23 of 2002 concerning Child Protection concerning physical violence committed against children as victims and in the general scope. 2) The application of criminal law in Decision Number 19/Pid.Sus-Anak/2018/PN Jkt.Pst., and Decision Number 00/Pid.Sus-Anak/2023/PN Jkt.Brt., is correct. The defendant has been proven legally and convincingly to fulfill the elements in Article 80 Paragraph (1) of Law Number 35 of 2014 concerning Amendments to Law Number 23 of 2002 concerning Child Protection. The judge considered that the defendant could be held responsible for the actions he had committed because he was in good health when he committed the crime, and there was no reason to remove the criminal sentence, so the Panel of Judges sentenced the Defendants to imprisonment.

Identification of a Novel RUNX1::STX2 Fusion in Mixed-Phenotype Acute Leukemia (MPAL) With BCR::ABL1.

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia (AL), MPAL with BCR::ABL1 fusion is the main subtype of MPAL, mainly affecting adult males. It is an acute leukemia with unique clinical and biological characteristics that involve both the myeloid and lymphatic systems. Gene fusion plays a crucial role in the pathogenesis, diagnosis, prognosis assessment, and treatment of leukemia. We present the first discovery of a novel fusion of RUNX1::STX2 in this subtype, which is co-expressed with BCR::ABL1 fusion. RUNX1 is a crucial transcription factor for hematopoietic differentiation, frequently found to be abnormal in AML, while STX2 may play a role in cancer progression. The RUNX1::STX2 fusion protein may act as the primary negative regulator of wild-type RUNX1, influencing normal cell differentiation and proliferation, consequently elevating the risk of leukemia. The gene fusion status of this patient is unique and complex, requiring further exploration to understand its functional significance in leukemia progression and treatment response.

Coordinated control strategy for improving frequency security of LCC[sbnd]HVDC sending-end system with large-scale wind power

To improve the frequency security of the LCCHVDC sending-end system with high penetration of wind power system and achieve optimal utilization of frequency regulation resources, a cooperative control strategy involving wind power and LCCHVDC in frequency regulation is proposed. Firstly, under a variety of scenarios, the power support requirements of LCCHVDC sending-end system are analyzed according to the power regulation margin of various frequency regulation resources and the disturbance power, and a multi-time scale frequency regulation control strategy for DFIG based wind farms is proposed, which combines the advantages of variable speed control and variable pitch angel control. And a cooperative control strategy of DFIG and LCCHVDC considering the frequency regulation deadband is proposed. Then, based on the maximum power regulation margin of synchronous generators and wind farms, the key control parameters of relative control links are designed to enable them autonomously adjust the active power according to various scenarios to involve in inertia response and primary frequency regulation task. Finally, the effectiveness of the control strategy is verified by the simulation model of LCCHVDC sending-end system with large-scale wind power, which significantly improves the frequency security and stability.

The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation.

The sebaceous gland (SG) is a vital appendage of the epidermis, and its normal homeostasis and function is crucial for effective maintenance of the skin barrier. Notch signaling is a well-known regulator of epidermal differentiation, and has also been shown to be involved in postnatal maintenance of SGs. However, the precise role of Notch signaling in regulating SG differentiation in the adult homeostatic skin remains unclear. While there is evidence to suggest that Notch1 is the primary Notch receptor involved in regulating the differentiation process, the ligand remains unknown. Using monoclonal therapeutic antibodies designed to specifically inhibit of each of the Notch ligands or receptors, we have identified the Jag2/Notch1 signaling axis as the primary regulator of sebocyte differentiation in mouse homeostatic skin. Mature sebocytes are lost upon specific inhibition of the Jag2 ligand or Notch1 receptor, resulting in the accumulation of proliferative stem/progenitor cells in the SG. Strikingly, this phenotype is reversible, as these stem/progenitor cells re-enter differentiation when the inhibition of Notch activity is lifted. Thus, Notch activity promotes correct sebocyte differentiation, and is required to restrict progenitor proliferation.

Identification of Hepatic-like Erythropoietin with Enhanced Activity As a New Cause of Hereditary and Acquired Erythrocytosis

Background:Hereditary and acquired erythrocytosis are characterized by increased red cell mass. They can develop secondary to disorders that cause tissue hypoxia or to an inappropriate increase in erythropoietin (EPO) production by interstitial kidney cells. EPO is the primary regulator of erythropoiesis during early fetal development and throughout adult life. Although EPO is produced in the fetal liver before birth, the major site of EPO production becomes the kidney shortly after birth.In this work, we identified six unrelated families with hereditary erythrocytosis associated with circulating EPO levels within the normal range, and characterized this condition as a novel molecular and functional entity.Methods:Luciferase reporter constructs were placed under the control of the mutant EPO regulatory elements to study the impact on EPO gene expression. Induced pluripotent stem cells (iPSC) were derived from patients' blood, which were differentiated into hepatocyte-like EPO-producing cells. EPO proteins from affected family members and healthy newborns were isolated from blood and analyzed by isoelectric focusing (IEF), then the activity of the purified EPO was quantified.Results:Using next-generation sequencing and segregation analysis, we identified three novel non-coding heterozygous mutations in the promoter and intron 1 of the EPO gene in the six families. Experiments with reporter assays and iPSC-derived hepatocyte-like cells showed that mutations target previously uncharacterized regulatory elements of the EPO gene that exhibit high responsiveness to HIF-2α. The circulating EPO protein from all patients with hereditary erythrocytosis examined in this study exhibited a unique and distinctive IEF profile compared to EPO produced by the kidneys of healthy adults. An identical IEF profile was also found in premature neonates, in whom EPO is produced by the liver, as well as in patients with acquired erythrocytosis associated with liver diseases. Interestingly, this profile, which shows a shift of the main EPO isoforms to a more basic region, was related to glycosylation modifications. This suggests lower contents of sialic acids and other modifications, indicating a liver-type glycosylation pattern, which differs from the classic kidney-type glycosylation pattern observed in adulthood. Finally, our functional assays of EPO protein purified from patients' plasma and umbilical cord blood revealed a statistically significant enhanced activity, as reflected by increased EPO receptor signaling in a human cell line, pointing to a potential gain-of-function for the liver-type glycosylation of EPO.Conclusions:We report a new entity of secondary erythrocytosis named Hepatic-like Erythropoietin Polycythemia (HEP), characterized by the production of liver-like EPO with an atypical glycosylation pattern and increased activity. This new form of EPO has been observed in all patients with hereditary EPO-mutated erythrocytosis, in cases of erythrocytosis associated with liver disease, and in neonates.Interestingly, the shift from a more active liver-type EPO to kidney-type EPO in newborns may explain the significant decrease in hemoglobin levels typically observed in the first weeks of life.Thus, it is essential to consider quantitative and qualitative EPO screening as part of the biological tests for the diagnosis of idiopathic and hereditary erythrocytosis.

The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation

The sebaceous gland (SG) is a vital appendage of the epidermis, and its normal homeostasis and function is crucial for effective maintenance of the skin barrier. Notch signaling is a well-known regulator of epidermal differentiation, and has also been shown to be involved in postnatal maintenance of SGs. However, the precise role of Notch signaling in regulating SG differentiation in the adult homeostatic skin remains unclear. While there is evidence to suggest that Notch1 is the primary Notch receptor involved in regulating the differentiation process, the ligand remains unknown. Using monoclonal therapeutic antibodies designed to specifically inhibit of each of the Notch ligands or receptors, we have identified the Jag2/Notch1 signaling axis as the primary regulator of sebocyte differentiation in mouse homeostatic skin. Mature sebocytes are lost upon specific inhibition of the Jag2 ligand or Notch1 receptor, resulting in the accumulation of proliferative stem/progenitor cells in the SG. Strikingly, this phenotype is reversible, as these stem/progenitor cells re-enter differentiation when the inhibition of Notch activity is lifted. Thus, Notch activity promotes correct sebocyte differentiation, and is required to restrict progenitor proliferation.

Modeling analysis and experiments of dual-FOV multiple scattering Raman lidar for detecting water cloud microphysical properties

Clouds are the primary regulators of the Earth’s climate, but the mechanisms through which they influence climate are poorly understood. Probing the microphysical properties of liquid water clouds is an urgent need for research on the Earth’s atmospheric system and atmospheric physics. In this paper, an iterative inversion of water cloud microphysical properties for a multiple scattering Raman lidar is presented, which can enable continuous, vertical measurements of the extinction coefficient of water clouds, the liquid water content (LWC), the effective radius of the cloud droplets, and cloud droplet number concentration (CDNC). The technique based on a constructed dual-field-of-view (dual-FOV) device combined with a quasi-small-angle (QSA) approximation model was investigated. The determination method of the optimal field of view (FOV) for lidar detection was discussed to enhance the sensitivity of the measured signals to the observed cloud microphysical parameters. Field observations with a co-located microwave radiometer (MWR) were carried out to verify the effectiveness of the lidar system, also an error analysis of the measurement examples was performed. The dual FOV Raman lidar experimental LWC measurement has an average deviation of 0.034 g/m3 and the relative error is 27.2% relative to the MWR measurement. The system has important potential applications in aerosol-cloud interactions and provides new ideas and methods for studying water cloud microphysical properties, further studying aerosol indirect effects.

Characterization of primary cilia in different epithelial cells of thyroid gland.

The primary cilium (PC) is a biosensor with diverse functions, depending on cellular type. In the thyroid, where it was first described, PCs are located at the apical pole of the follicular epithelium, sensing the lumen's environment. They probably contribute to follicular homeostasis, although their presence in other thyroid epithelial cells remains unclear. Thyroglobulin, stored in the lumen as colloid, is the primary regulator of thyroid-specific gene expression under constant TSH levels. The mechanism by which thyroglobulin signal is transduced remains unresolved. This study investigates the evolution of PCs in different types of thyroid follicles, based on their functional activity, using both normal human thyroids and functional thyroid pathologies as models. It also compares PC morphology between human and rat thyrocytes and explores their presence in other thyroid epithelial components such as C cells and ultimobranchial remnants. Human and Wistar rat thyroid tissues were analyzed using histological, immunohistochemical, immunofluorescence, and electron microscopy techniques. Morphometric analyses quantified PC changes (frequency and length) in various follicular patterns, and statistical analyses were performed. Four types of thyroid follicles were identified: active, hyperactive, hypoactive, and empty follicles. PCs were most abundant and longest in active and significantly reduced in empty follicles. PCs were more prominent in human than in rat thyrocytes, present in both normal and neoplastic C cells, but sporadic in ultimobranchial remnants. PCs vary according to follicular activity and likely act as mechanosensors in thyroid hormone regulation, detecting colloid density and contributing to the regulation of thyroid hormone biosynthesis.

The enhancement of primary frequency regulation ability of combined water and power plant based on nuclear energy: Dynamic modelling and control strategy optimization

The combined water and power plant based on nuclear energy (CWPN) is a potential way with significant economic and environmental benefits. To accommodate high penetration of intermittent renewable power within the power grid, it is essential to enhance the primary frequency regulation (PFR) ability of CWPN, and many factors, including the reactor operation safety, energy efficiency, and the water-power coupling mechanism of CWPN should be considered. In this study, a dynamic model of CWPN was developed, and two new strategies, the constant turbine power method (CPM) and the classic-PI-decoupling method (CDM), were proposed to enhance PFR capability. The results show that both strategies maintain the reactor power at full load during PFR, with CDM providing superior control, as evidenced by a maximum overshoot of 0.56 % compared with 3.58 % for CPM. Under typical step disturbances of ±1 % full power (FP), ±2%FP, and ±3%FP, the PFR performance of the original and new strategies was evaluated on the basis of settling time and the apex/nadir frequency. Compared with the original strategy (OS), the maximum settling time under CDM and CPM was reduced by 3.3 s and 8.8 s, respectively. The proposed strategies demonstrated improved PFR performance, with smaller apex/nadir frequency values than those of the OS.

Molecular docking and molecular dynamics of hypoxia-inducible factor (HIF-1alpha): towards potential inhibitors

HIF-1α is a primary regulator in the adaptation of cancer cells to hypoxia. The aim was to find out new inhibitors of the HIF-1α. A molecular dynamic (MD) simulation performed on HIF-1α showed stable dynamic features. Virtual screening of 217 anticancer drugs was performed along with a positive control (2-Methoxyestradiolm, 2-ME2) on an optimized HIF-1α and dynamically simulated structure. Docking results produced two compounds namely pycnidione and nilotinib of high binding affinity −9.34 kcal/mol and −9.04 kcal/mol respectively, whereas 2-ME2 displayed a relatively lower affinity (-6.68 kcal/mol). For the three complexes, MD of 200 ns simulation was run. Data analysis showed that the three medications behaved similarly in the MD simulation. Nilotinib had a lower RMSD and higher SASA than the other complexes. In addition, the Nilotinib-HIF-1α combination had a lower RMSF value, a flatter Rg, and a number of hydrogen bonds similar to other complexes. MM-GBSA analysis revealed that nilotinib, pycnidione and 2-ME2 compounds had free binding energy of −23.77 ± 5.29, −21.85 ± 4.24 and −7.53 ± 6.62 kcal/mol respectively. Nilotinib and pycnidione bind competitively to HIF-1α, with nilotinib showing consistent molecular-dynamic properties. They relatively pass the blood-brain barrier, non-carcinogenic, and have IV-category acute oral toxicity. They have low CYP inhibitory characteristics. Further investigations are therefore warranted to elucidate their implications in hypoxia pathways, cell proliferation, apoptosis, survival, and metastatic potential.

YAP Signaling in Glia: Pivotal Roles in Neurological Development, Regeneration and Diseases.

Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.

Study on improved control strategy of virtual synchronous generator

Virtual synchronous generator (VSG) control technology for photovoltaic, energy storage, wind power, and other new energy to provide flexibility in the grid interface characteristics, is conducive to improving the stability of the power system, and has been widely considered by many scholars. Firstly, an improved VSG control method is proposed through simulation and analysis, which realizes the complete decoupling of the frequency response time constant and the inertia quantity of the active power control loop and reduces the complexity of the parameter design of the VSG system. Secondly, to avoid the frequent action of the VSG system caused by small-scale frequency change perturbation, this study proposes a VSG frequency optimization control method for VSG frequency control with rated angular velocity ωset feedforward composed of multivariate factors when considering a primary frequency regulation dead zone. Thirdly, the impact of VSG parameter design on the system is investigated through the system response characteristics of power scheduling, primary frequency regulation at the grid connection, and the small-signal dynamic characterization of the improved VSG. Finally, Simulation and experimental verification yielded an active power overshoot of 7% and a maximum frequency deviation of 0.17 Hz for the improved system. The improved control method resulted in an improvement of 0.1 s in the frequency response time and a reduction of 0.15 Hz in the oscillation amplitude. The response speed of the improved control method is much better, while the oscillation amplitude is reduced to meet the grid's regulation requirements. The simulation and experimental analysis verify the feasibility of the improved VSG control method.

Genetic Screening Reveals Cone Cell-Specific Factors as Common Genetic Targets Modulating Rival-Induced Prolonged Mating in male Drosophila melanogaster.

Male-male social interactions exert a substantial impact on the transcriptional regulation of genes associated with aggression and mating behavior in male Drosophila melanogaster. Throughout our comprehensive genetic screening of aggression-related genes, we identified that the majority of mutants for these genes are associated with rival-induced and visually-oriented mating behavior, longer-mating-duration (LMD). The majority of mutants with upregulated genes in single-housed males significantly altered LMD behavior but not copulation latency, suggesting a primary regulation of mating duration. Single-cell RNA sequencing revealed that LMD-related genes are predominantly co-expressed with male-specific genes like dsx and Cyp6a20 in specific cell populations, especially in cone cells. Functional validation confirmed the roles of these genes in mediating LMD. Expression of LMD genes like Cyp6a20, Cyp4d21, and CrzR was enriched in cone cells, with disruptions in cone cell-specific expression of CrzR and Cyp4d21 leading to disrupted LMD. We also identified a novel gene, CG10026/Macewindu, that reversed LMD when overexpressed in cone cells. These findings underscore the critical role of cone cells as a pivotal site for the expression of genes involved in the regulation of LMD behavior. This study provides valuable insights into the intricate mechanisms underlying complex sexual behaviors in Drosophila.

Study on adaptive VSG parameters and SOC control strategy for PV-HESS primary frequency regulation

Hybrid energy storage plays a critical role in primary frequency regulation during large-scale renewable energy integration. Rational power distribution between multiple types of energy storage, as well as the use of a VSG control technique, are effective approaches to improving primary frequency regulation capability. To that end, this paper presents an adaptive Virtual Synchronous Generator (VSG) characteristics and state of charge (SOC) management technique for photovoltaic (PV) - hybrid energy storage system (HESS) primary frequency regulation. First, a power distribution mechanism for HESS on the direct current side is implemented. Second, a primary frequency control strategy is proposed based on adaptive rotational inertia and damping coefficient of VSG and SOC regulation of energy storage. Finally, a simulation analysis confirms the feasibility of the proposed primary frequency control strategy under transient conditions. The relevant results are presented as follows. Compared to traditional control strategies, the improved adaptive VSG parameter and energy storage SOC control strategy reduces the overshoot and adjustment time of VSG active power and frequency response by 68.57%, 23.94%, 19.05% and 9.80%, respectively. The decline in SOC of battery energy storage is decreased by 3.18%. The proposed control strategy also limits grid frequency fluctuation within ±0.2 Hz, with a recovery time of less than 0.5 seconds. The overall root mean square error of frequency fRMSE is a maximum of 0.02 Hz. The primary frequency regulation capability of the PV-HESS is enhanced, ensuring the operational safety of energy storage systems and effectively improving the stability while also improving grid stability and security.

A primary joint frequency regulation strategy for wind-thermal-storage systems considering frequency regulation deadband

Abstract For the issue of system frequency stability in low-inertia regions, a primary joint frequency regulation strategy for wind-thermal-storage systems considering frequency regulation deadbands is proposed. First, a system frequency response model incorporating wind-storage frequency regulation deadbands is constructed to analyze the dynamic impact of deadband variations on grid frequency. Next, the timing of frequency regulation actions in the wind-storage system is determined by manually setting the frequency regulation deadband. Finally, the effectiveness of the proposed strategy is validated using a large disturbance excitation method.

Targeted CRISPR regulation of ZNF865 enhances stem cell cartilage deposition, tissue maturation rates, and mechanical properties in engineered intervertebral discs

Cell and tissue engineering based approaches have garnered significant interest for treating intervertebral disc degeneration and associated low back pain due to the substantial limitations of currently available clinical treatments. Herein we present a clustered regularly interspaced short palindromic repeats (CRISPR)-guided gene modulation strategy to improve the therapeutic potential of cell and tissue engineering therapies for treating intervertebral disc disease. Recently, we discovered a zinc finger (ZNF) protein, ZNF865 (BLST), which is associated with no in-depth publications and has not been functionally characterized. Utilizing CRISPR-guided gene modulation, we show that ZNF865 regulates cell cycle progression and protein processing. As a result, regulating this gene acts as a primary titratable regulator of cell activity. We also demonstrate that targeted ZNF865 regulation can enhance protein production and fibrocartilage-like matrix deposition in human adipose-derived stem cells (hASCs). Furthermore, we demonstrate CRISPR-engineered hASCs ability to increase GAG and collagen II matrix deposition in human-size tissue-engineered discs by 8.5-fold and 88.6-fold, respectively, while not increasing collagen X expression compared to naive hASCs dosed with growth factors. With this increased tissue deposition, we observe significant improvements in compressive mechanical properties, generating a stiffer and more robust tissue. Overall, we present novel biology on ZNF865 and display the power of CRISPR-cell engineering to enhance strategies treating musculoskeletal disease. Statement of significanceThis work reports on a novel gene, ZNF865 (also known as BLST), that when regulated with CRISPRa, improves cartilagenous tissue deposition in human sized tissue engineering constructs. Producing tissue engineering constructs at human scale has proven difficult, and this strategy presents a broadly applicable tool to enhance a cells ability to produce tissue at these scales, as we saw an ∼8–88 fold increase in tissue deposition and significantly improved biomechanics in large tissue engineered intervertebral disc compared to traditional growth factor differentiation methods. Additionally, this work begins to elucidate the biology of this novel zinc finger protein, which appears to be critical in regulating cell function and activity.

Revolutionizing Infertility Management through Novel Peptide-based Targets.

Around 48 million couples and 186 million people worldwide have infertility; of these, approximately 85% have an identifiable cause, the most common being ovulatory dysfunctions, male infertility, polycystic ovary syndrome, and tubule disease. The remaining 15% have infertility for unknown reasons, including lifestyle and environmental factors. The regulation of the hypothalamic- pituitary-adrenal axis (HPA) is crucial for the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which are essential for female reproductive functions. GnRH is the primary reproductive axis regulator. The pattern of GnRH, FSH, and LH release is determined by its pulsatile secretion, which in turn controls endocrine function and gamete maturation in the gonads. Peptides called Kisspeptin (KP), Neurokinin-B (NKB), and Orexin influence both positive and negative feedback modulation of GnRH, FSH, and LH secretion in reproduction. This review article mainly focuses on the historical perspective, isoform, and signaling pathways of KP, NKB, and Orexin novel peptide-based targets including clinical and preclinical studies and having a promising effect in the management of infertility.

The study of active support for energy storage system in system frequency regulation

Abstract As the penetration of new energy sources increases, the proportion of traditional energy units continues to decline, reducing the inertia and primary frequency regulation capability of the power system. Therefore, exploring the frequency support capabilities of energy storage systems with low inertia is crucial. Based on this, this paper first proposes an active frequency support method for energy storage system based on a Voltage Source Virtual Synchronous Generator (VSG), aiming to enhance system inertia and reduce response delay. Based on this issue, a parameter tuning optimization selection model based on the Transient Search Optimization (TSO) algorithm is proposed to determine the optimal power output and best frequency regulation parameters for the energy storage system. Finally, the model proposed in this paper is applied to the IEEE 14-bus system to verify its effectiveness.

Duration of morning hyperinsulinemia determines hepatic glucose uptake and glycogen storage later in the day.

The second-meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 h of morning hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon hyperinsulinemic-hyperglycemic (HIHG) clamp. Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the afternoon response to a HIHG clamp. To determine this, the same total amount of insulin was administered either over 2 h in the first (Ins2h-A) or second (Ins2h-B) half of the morning or over the entire 4 h (Ins4h) of the morning. In the 4-h afternoon period, all three groups had 4x-basal insulin, 2x-basal glycemia, and portal glucose infusion to expose the liver to the primary postprandial regulators of hepatic glucose metabolism. During the afternoon clamp, there was a marked increase in HGU and hepatic glycogen synthesis in the Ins4h group compared with the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose loads and total insulin infusion rates. Thus, the longer duration (Ins4h) of lower hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the afternoon clamp.NEW & NOTEWORTHY Morning insulin exposure primes the liver for increased hepatic glucose uptake and glycogen storage during a subsequent hyperinsulinemic-hyperglycemic clamp. This study addressed whether the pattern and/or duration of insulin delivery in the morning influences insulin's ensuing priming effect. We found that despite receiving equal total doses of insulin in the morning, a prolonged, lower rate of morning insulin delivery improved afternoon liver glucose metabolism more effectively than a shorter, higher rate of delivery.

Impact of fleQ Deficiency on Resource Allocation and Heterologous Gene Expression in Pseudomonas putida Across Various Growth Media.

Pseudomonas putida is widely used in industrial applications, including the recombinant proteins production, because of its natural advantageous properties. In this study, the gene encoding FleQ, the primary regulator of flagellar synthesis, was deleted to construct a new non-motile P. putida KT2440-derived strain (ΔfleQ). The non-motile cells showed reduced biofilm formation and enhanced expression of a heterologous gene in nutrient-rich media compared with the wild-type (WT) strain, attributed to the reallocation of cellular resources from flagellar synthesis and cellular motility. Additionally, the ΔfleQ strain exhibited enhanced tolerance to chloramphenicol, indicating higher ribosome production, confirmed by a higher RNA/protein ratio relative to the WT. While the WT strain showed decreased growth and a three-fold increase in reporter gene activity in minimal media, the ΔfleQ strain maintained consistent reporter gene expression and exhibited a relatively higher growth rate. This suggests that the FleQ is involved in modulating proteome allocation based on nutrient quality. The removal of FleQ allows for more flexible resource allocation, creating a chassis strain with nutrient quality-independent gene expression capacity, which could be valuable in industrial applications where consistent output is essential.